B-cell Acute Lymphoblastic Leukemia, Refractory B-cell Acute Lymphoblastic Leukemia, Relapsed B-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
relapsed/refractory, Philadelphia chromosome positive acute lymphoblastic leukemia, Pharmaceuticals, Philadelphia chromosome positive, Acute Lymphoid Leukemia (ALL), Acute Lymphocytic Leukemia (ALL), CTL019, tisagenlecleucel
Brief summary
This was a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of an experimental therapy called CTL019 T-cells in pediatric patients with B-cell acute lymphoblastic leukemia, who were refractory to standard chemotherapy regimen or relapsed after allogeneic stem cell transplant.
Interventions
BIOLOGICALCTL019 T-cells
A target dose of CTL019 transduced cells will consist of a single infusion of 2.0 to 5.0 x 10\^6 CTL019 transduced cells per kg body weight (for patients ≤ 50 kg) and 1.0 to 2.5 x 10\^8 CTL019 transduced viable T cells (for patients \> 50 kg). The following cell dose ranges may be infused if all other safety release criteria are met: 0.2 to 5.0 x 10\^6 CTL019 transduced viable T cells per kg body weight (for patient ≤ 50 kg) and 0.1 to 2.5 x 10\^8 CTL019 transduced viable T cells (for patients \> 50 kg).
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Relapsed or refractory pediatric B-cell ALL and lymphoblastic lymphoma: 1. 2nd or greater Bone Marrow (BM) relapse OR 2. Any BM relapse after allogeneic SCT and must be \> 6 months from SCT at the time of CTL019 infusion OR 3. Refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapse leukemia OR 4. Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI), or if TKI therapy is contraindicated OR 5. Ineligible for allogeneic SCT * For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of study entry * Adequate organ function defined as: 1. Renal function defined as (Calculated creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) \> 60 mL/min/1.73 m2 OR serum creatinine based on age/gender 2. Alanine Aminotransferase (ALT) \<= 5 times the upper limit of normal (ULN) for age; 3. Bilirubin \< 2.0 mg/dL; 4. Must have a minimum level of pulmonary reserve defined as ≤Grade 1 dyspnea and pulse oxygenation \> 91% on room air 5. Left Ventricular Shortening Fraction (LVSF) ≥ 28% confirmed by echocardiogram, or Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or MUGA within 7 days of screening * Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening * Life expectancy \> 12 weeks * Age 3 at the time of screening per protocol to age 21 at the time of initial diagnosis * Karnofsky (age ≥ 16 years) or Lansky (age \< 16 years) performance status ≥ 50 at screening * Signed written informed consent and assent forms (if applicable) must be obtained prior to any study procedures * Once all other eligibility criteria are confirmed, must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site. Note: Apheresis product will not be shipped to or assessed for acceptance by the manufacturing site until documented confirmation of all other eligibility criteria is received. * Patients with active CNS leukemia involvement defined as CNS-3 by CSF findings only are eligible but will have their CTL019 infusion delayed until CNS disease is reduced to CNS-1 or CNS-2 by CSF findings. Patients with other forms of active CNS-3 leukemic involvement such as CNS parenchymal or ocular disease, cranial nerve involvement or significant leptomeningeal disease are not eligible. However, such patients with other forms of CNS-3 leukemic involvement (non-CSF involvement) are eligible if there is documented evidence of disease stabilization for at least 3 months prior to CTL019 infusion. Patients must have no acute/ongoing neurologic toxicity \> Grade 1 with the exception of a history of controlled seizures or fixed neurologic deficits that have been stable/improving over the past 3 months.
Exclusion criteria
* Isolated extra-medullary disease relapse * Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded. * Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell \[surface Immunoglobulin (sIg) positive and kappa or lambda restricted positivity\] ALL, with FAB L3 morphology and /or a MYC translocation) * Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease * Prior treatment with gene therapy product * Treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy * Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD) * Patient has participated in an investigational research study using an investigational agent within the last 30 days prior to screening * Pregnant or nursing (lactating) women. NOTE: female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion * Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening * HIV positive test within 8 weeks of screening * The following medications are excluded: 1. Steroids: Therapeutic systemic doses of steroids must be stopped \> 72 hours prior to CTL019 infusion. However, the following physiological replacement doses of steroids are allowed: \< 12 mg/m2/day hydrocortisone or equivalent 2. Allogeneic cellular therapy: Any donor lymphocyte infusions (DLI) must be completed \> 6 weeks prior to CTL019 infusion 3. GVHD therapies: Any systemic drug used for GVHD must be stopped \> 4 weeks prior to CTL019 infusion to confirm that GVHD recurrence is not observed (e.g. calcineurin inhibitors, methotrexate or other chemotherapy drugs, mycophenolate, rapamycin, thalidomide, or immunosuppressive antibodies such as anti-CD20 (rituximab), anti-tumor necrosis factor \[anti-TNF\], anti-interleukin 6 \[anti-IL6\] or anti-interleukin 6 receptor \[anti-IL6R\], systemic steroids) 4. Chemotherapy: * Tyrosine kinase inhibitors and hydroxyurea must be stopped \> 72 hours prior to CTL019 infusion * The following drugs must be stopped \> 1 week prior to CTL019 infusion and should not be administered concomitantly or following lymphodepleting chemotherapy: vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate \< 25 mg/m2, cytosine arabinoside \< 100 mg/m2/day, asparaginase (non-pegylated) * The following drugs must be stopped \>2 weeks prior to CTL019 infusion: salvage chemotherapy (e.g. clofarabine, cytosine arabinoside \> 100 mg/m2, anthracyclines, cyclophosphamide, methotrexate ≥ 25 mg/m2), excluding the required lymphodepleting chemotherapy drugs * Pegylated-asparaginase must be stopped \> 4 weeks prior to CTL019 infusion e. CNS disease prophylaxis: * CNS prophylaxis treatment must be stopped \> 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate) f. Radiotherapy: * Non-CNS site of radiation must be completed \> 2 weeks prior to CTL019 infusion * CNS directed radiation must be completed \> 8 weeks prior to CTL019 infusion g. Anti T-cell Antibodies: Administration of any T cell lytic or toxic antibody (e.g. alemtuzumab) within 8 weeks prior to CTL019 is prohibited since residual lytic levels may destroy the infused CTL019 cells and/or prevent their in vivo expansion. If such an agent has been administered within 8 weeks prior to CTL019, contact the Sponsor, consider consultation with an pharmacology expert, and consider measuring residual drug levels, if feasible, prior to CTL019 infusion Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants, unless they are using highly effective methods of contraception for a period of 1 year after the CTL019 infusion. Highly effective contraception methods include: 1. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are NOT acceptable methods of contraception 2. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment 3. Male sterilization (at least 6 months prior to screening). For female patients on the study the vasectomized male partner should be the sole partner for that patient 4. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception 5. Use of IUDs are excluded due to increased risks of infection and bleeding in this population. However, IUD inserted prior to consent may remain in place, and a second method of contraception is mandated 6. In case of use of oral contraception, women must be stable on the same pill for a minimum of 3 months before taking study treatment. Women who are not of reproductive potential (defined as either \<11 years of age, Tanner Stage 1, post-menopausal for at least 24 consecutive months (i.e. have had no menses) or have undergone hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy) are eligible without requiring the use of contraception. Women who are not yet of reproductive potential are to agree to use acceptable forms of contraception when they reach reproductive potential if within 1 year of CTL019 or if CAR cells are present in the blood by PCR. Acceptable documentation includes written or oral documentation communicated by clinician or clinician's staff of one of the following: 1. Demographics show age \< 11 2. Physical examination indicates Tanner Stage 1 3. Physician report/letter 4. Operative report or other source documentation in the patient record 5. Discharge summary 6. Follicle stimulating hormone measurement elevated into the menopausal range
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Remission Rate (ORR) Per Independent Review Committee (IRC) (for ALL Participants) | within 6 months after CTL019 infusion | ORR is defined as the percentage of participants with a best overall disease response of complete remission (CR) or Complete remission with incomplete blood count recovery (CRi), where the best overall disease response is defined as the best disease response recorded from CTL019 infusion until the start of new anticancer therapy. Best response was assigned in the following order: CR, CRi, CR or CRi with residual mediastinal disease, No response and Unknown. |
| Overall Remission Rate (ORR) Per Local Investigator Assessment (for Lymphoblastic Lymphoma Patients Only) | 6 months after CTL019 | Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi), as determined by assessments of peripheral blood, bone marrow, CNS symptoms, physical exam (PE) and cerebrospinal fluid (CSF). This primary endpoint was based on the local investigator assessment. No participants with lymphoblastic lymphoma were infused in this study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Remission (DOR) Per Local and IRC Assessment | From CR or CRi to relapse or death up to 60 months | DOR is the time from achievement of CR or CRi, whichever occurs first, to relapse or death due to ALL |
| Percentage of Participants With CR or CRi With Minimum Residual Disease (MRD) Negative Bone Marrow 6 Months After CTL019 Infusion | within 6 months | Percentage of participants with best overall response (BOR) of CR or CRi with MRD negative bone marrow status 6 months after CTL019 infusion among all participants who achieved CR or CRi per Local Investigator & IRC assessment |
| Relapse-free Survival (RFS) for Responders Per Local and IRC Assessment | 60 Months | RFS is the time from achievement of CR or CRi whichever occurs first to relapse or death due to any cause during CR or CRi. |
| Event-free Survival (EFS) Per Local and IRC Assessment | 60 Months | EFS is the time from date of CTL019 infusion to the earliest of death, relapse or treatment failure. Treatment failure is defined as no response in the study and discontinuation from the study due to any of the following reasons: death, AE, lack of efficacy, new anticancer therapy. |
| Overall Survival (OS) | 60 Months | OS is the time from date of CTL019 infusion to the date of death due to any reason |
| Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion | Day 28 | Percentage of participants attaining CR or CRi with MRD negative bone marrow status at Day 28 +/- 4 days after CTL019 infusion per Local Investigator and IRC assessment. BM MRD were only collected and measured only within responders. |
| CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Enrollment; D1; D4; D7; D11; D14; D21; D28; M3; M6; M9, M12; M18; M24, M30, M36, M42, M48 for transgene levels in blood; Screening, D28, M3, M6 for transgene levels in bone marrow | Characterize the in vivo cellular pharmacokinetic (PK) profile (levels,persistence, trafficking) of CTL019 cells in target tissues |
| Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Baseline; Day 14; Day 28; Month 3; Month 6; Month 12; Month 24, Month 36 | Humoral immunogenicity was measured by anti-CTL019 antibodies in human serum using a flow cytometry method. (Prevalence and incidence of immunogenicity to CTL019) |
| ORR by Low Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion | Within 6 months | ORR within 6 months after infusion of CTL019 per Local & IRC assessment by baseline bone marrow tumor burden presence. |
| ORR by High Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion | Within 6 months | ORR within 6 months after infusion of CTL019 per Local Investigator & IRC assessment by high baseline bone marrow tumor burden presence. |
| ORR by Baseline Extramedullary Disease Presence of Yes Within 6 Months Post CTL019 Infusion | Within 6 months | ORR within 6 months after infusion of CTL019 per Local Investigator & IRC assessment by baseline extramedullary disease presence of Yes. |
| ORR by Baseline Extramedullary Disease Presence of No Within 6 Months Post CTL019 Infusion | Within 6 months | ORR within 6 months after infusion of CTL019 per Local Investigator & IRC assessment by baseline extramedullary disease presence of No. |
| Bone Marrow (BM) Minimum Residual Disease (MRD) Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by High Baseline Bone Marrow Tumor Burden | Within 6 months | BM MRD status was by Local Investigator and IRC assessment within 6 months after infusion of CTL019 by baseline bone marrow tumor burden. BM MRD were collected and measured only within responders. |
| Bone Marrow MRD Status Was by Flow Cytometry Within 6 Months Post CTL019 Infusion by Low Baseline Bone Marrow Tumor Burden | Within 6 months | BM MRD status was per Local Investigator and IRC assessment within 6 months after infusion of CTL019 by low baseline bone marrow tumor burden. BM MRD were collected and measured only within responders. |
| Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: Yes | Within 6 months | BM MRD status was by Local Investigator and IRC assessment within 6 months after infusion pf CTL019 by baseline extramedullary disease presence of Yes. BM MRD were collected and measured only within responders. |
| Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: No | Within 6 months | BM MRD status WAS per Local Investigator and IRC assessment within 6 months after infusion pf CTL019 by baseline extramedullary disease presence of No. BM MRD were collected and measured only within responders. |
| Duration of Remission (DoR) Censoring Hematopoietic Stem Cell Transplantation (HSCT) by Low Baseline Bone Marrow Tumor Burden | Within 6 months | DoR per Local Investigator & IRC assessment by low baseline marrow tumor burden |
| Duration of Remission (DoR) Censoring HSCT by High Baseline Bone Marrow Tumor Burden | Within 6 months | DoR per Local Investigator & IRC assessment by high baseline bone marrow tumor burden |
| Percentage of Participants With Clinical Response Without Stem Cell Transplantation (SCT) at Month 6 - Per IRC Assessment | Month 6 | Evaluate the percentage of participants who achieved CR or CRi at Month 6 without SCT between tisagenlecleucel infusion and Month 6 response assessment. |
| Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: No | Within 6 months | DoR per Local Investigator & IRC assessment by baseline extramedullary disease presence of No |
| Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tlast | Day 28 | Characterize the in vivo cellular pharmacokinetic (PK) profile. Tlast is defined as the time of last observed quantifiable concentration in peripheral blood (days) |
| Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline; Day 14; Day 28; Month 3; Month 6; Month 12; Month 24, Month 36 | Activation of T cells in PBMC collected from subjects in response to mCAR19 -derived peptides was used to assess the cellular immunogenicity against tisagenlecleucel. CD4 and CD8 T cell net responses (in %) were calculated for 2 non-overlapping CTL019 peptide pools (i.e., Pool 1 and Pool 2). (Lymphocyte subsets of B and T cells and description of associated safety events) |
| Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: AUC0-28d and AUC0-84d | 0 - 28 days post-infusion for AUC0-28d and 0 - 84 days post-infusion for AUC0-84d | Characterize the in vivo cellular pharmacokinetic (PK) profile. AUC0-28d and AUC0-84d is defined as the AUC from time zero to day 28 and 84 or other disease assessment days, in peripheral blood (% or copies/μg x days). Data was only reported for evaluable PK parameters. The Overall Number of Participants Analyzed represents all participants for which a baseline assessment was collected for this Outcome Measure, and therefore these participants did contribute data to this estimation parameter, whereas the Number Analyzed per Row represents the number of participants with data available at either 28 or 84 days. |
| Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Cmax | Day 28 | Characterize the in vivo cellular pharmacokinetic (PK) profile. Cmax is defined as the maximum (peak) observed in peripheral blood drug concentration after single dose administration (% or copies/μg). |
| Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tmax | Day 28 | Characterize the in vivo cellular pharmacokinetic (PK) profile. Tmax is defined as the time to reach maximum (peak) peripheral blood drug concentration after single dose administration (days) |
| Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: T1/2 | Day 28 | Characterize the in vivo cellular pharmacokinetic (PK) profile. T1/2 is defined as the half-life associated with the disposition phase slopes (alpha, beta, gamma etc.) of a semi logarithmic concentration-time curve (days) in peripheral blood |
| Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Clast | Day 28 | Characterize the in vivo cellular pharmacokinetic (PK) profile. Clast is defined as the last observed quantifiable concentration in peripheral blood (% or copies/ug) |
| CD19 Status of Bone Marrow/Blood Relapse in FAS Patients Who Achieved CR or CRi and Then Relapsed | At time of relapse up to 60 months | The CD19 status of bone marrow/blood relapse was categorized as follows: CD19 positive, CD19 dim, CD19 negative, CD19 positive/negative & CD19 unknown |
| Site of Initial Relapse Among FAS Patients Who Achieved CR/CRi and Then Relapsed | At time of relapse up to 60 months | This is the site of involvement of initial relapse after achieving a best overall response of CR/CRi. |
| Time to B-cell Recovery in Participants Who Achieved CR or CRi by IRC | during the whole study, up to 60 months | Time to B cell recovery was defined as the time from onset of remission to the earliest time when the percentage of CD19+ total B cell among viable WBC is ≥ 1% or among lymphocyte is at least 3%. |
| Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Enrollment/Pre-Chemotherapy; Pre-infusion; Baseline; Day 7; Day 14; Day 21; Day 28; Month 3; Month 6; Month 9; Month 12; Month 24; Month 36 | The levels (%) of CD19+ total B cells amongst viable white blood cells (WBC) in peripheral blood |
| Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3 | C-Reactive Protein at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3 |
| Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3 | Ferritin at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3 |
| Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3 | INF-gamma at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3 |
| Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3 | IL-6 at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3 |
| Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3 | IL-2 at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3 |
| Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: Yes | Within 6 months | DoR per Local Investigator & IRC assessment by baseline extramedullary disease presence of Yes. |
| Percentage of Subjects Who Achieved CR or CRi and Then Proceeded to SCT While in Remission Prior to Month 6 Response - Per IRC Assessment | prior to Month 6 | Evaluate the percentage of subjects who achieved CR or CRi and then proceeded to SCT while in remission prior to Month 6 response assessment. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited between 14-Aug-2014 (FPFV) and 22-Sep-2017 (LPFV). At the time of LPLV (24-May-2019), the sponsor had decided to transfer all ongoing patients to a separate long-term follow-up study to complete the planned 15 years of follow-up. These patients are designated with the reason for discontinuation as terminated by sponsor.
Pre-assignment details
Enrolled means all eligibility criteria were met and apheresis was accepted by the manufacturing facility. Patients could discontinue the trial after enrollment and prior to tisagenlecleucel infusion. Although 75 patients were enrolled, only 64 were infused as 11 discontinued prior to infusion.
Participants by arm
| Arm | Count |
|---|---|
| Tisagenlecleucel (CTL019) - All Participants Pediatric participants with r/r B-cell who were infused with tisagenlecleucel | 64 |
| Not Infused Pediatric patients with r/r B-cell who were enrolled in the study but not infused with tisagenlecleucel | 11 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 12 |
| Overall Study | Enrolled, not infused | 11 |
| Overall Study | Lack of Efficacy | 18 |
| Overall Study | New therapy for study indication | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Study terminated by Sponsor | 24 |
| Overall Study | Subject/guardian decision | 2 |
Baseline characteristics
| Characteristic | Tisagenlecleucel (CTL019) - All Participants | Total | Not Infused |
|---|---|---|---|
| Age, Continuous | 12.4 Years STANDARD_DEVIATION 5.16 | 12.8 Years STANDARD_DEVIATION 5.26 | 15.2 Years STANDARD_DEVIATION 5.44 |
| Karnofsky/Lansky performance status 100 | 18 Participants | 18 Participants | — |
| Karnofsky/Lansky performance status 50 | 2 Participants | 2 Participants | — |
| Karnofsky/Lansky performance status 60 | 1 Participants | 1 Participants | — |
| Karnofsky/Lansky performance status 70 | 2 Participants | 2 Participants | — |
| Karnofsky/Lansky performance status 80 | 13 Participants | 13 Participants | — |
| Karnofsky/Lansky performance status 90 | 28 Participants | 28 Participants | — |
| Karnofsky/Lansky performance status less than 50 | 0 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Asian | 5 participants | 6 participants | 1 participants |
| Race/Ethnicity, Customized Other | 7 participants | 9 participants | 2 participants |
| Race/Ethnicity, Customized White | 52 participants | 60 participants | 8 participants |
| Sex: Female, Male Female | 34 Participants | 35 Participants | 1 Participants |
| Sex: Female, Male Male | 30 Participants | 40 Participants | 10 Participants |
| Weight | 43.7 kg STANDARD_DEVIATION 20.1 | 47.3 kg STANDARD_DEVIATION 25.25 | 86.2 kg STANDARD_DEVIATION 41.52 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 30 / 64 |
| other Total, other adverse events | 64 / 64 |
| serious Total, serious adverse events | 52 / 64 |
Outcome results
Primary
Overall Remission Rate (ORR) Per Independent Review Committee (IRC) (for ALL Participants)
ORR is defined as the percentage of participants with a best overall disease response of complete remission (CR) or Complete remission with incomplete blood count recovery (CRi), where the best overall disease response is defined as the best disease response recorded from CTL019 infusion until the start of new anticancer therapy. Best response was assigned in the following order: CR, CRi, CR or CRi with residual mediastinal disease, No response and Unknown.
Time frame: within 6 months after CTL019 infusion
Population: Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Overall Remission Rate (ORR) Per Independent Review Committee (IRC) (for ALL Participants) | 70.3 Percentage of participants |
p-value: <0.0001Clopper-Pearson
Primary
Overall Remission Rate (ORR) Per Local Investigator Assessment (for Lymphoblastic Lymphoma Patients Only)
Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi), as determined by assessments of peripheral blood, bone marrow, CNS symptoms, physical exam (PE) and cerebrospinal fluid (CSF). This primary endpoint was based on the local investigator assessment. No participants with lymphoblastic lymphoma were infused in this study.
Time frame: 6 months after CTL019
Population: Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS. No patients with Lymphoblastic Lymphoma were enrolled in this trial, hence there is no data to report.
Secondary
Bone Marrow (BM) Minimum Residual Disease (MRD) Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by High Baseline Bone Marrow Tumor Burden
BM MRD status was by Local Investigator and IRC assessment within 6 months after infusion of CTL019 by baseline bone marrow tumor burden. BM MRD were collected and measured only within responders.
Time frame: Within 6 months
Population: Efficacy Analysis Set: A subset of FAS treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on cut-off date of 6-Oct-2017, with only 42 participants and 30 having a high baseline bone marrow tumor burden. BM MRD were collected and measured only within responders
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Bone Marrow (BM) Minimum Residual Disease (MRD) Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by High Baseline Bone Marrow Tumor Burden | Had BOR of CR/CRi with BM MRD -ve (MRD%< 0.01%) | 56.7 percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Bone Marrow (BM) Minimum Residual Disease (MRD) Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by High Baseline Bone Marrow Tumor Burden | Had BOR of CR/CRi with BM 0.01% <= MRD% < 5% | 6.7 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Bone Marrow (BM) Minimum Residual Disease (MRD) Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by High Baseline Bone Marrow Tumor Burden | Had BOR of CR/CRi with BM MRD -ve (MRD%< 0.01%) | 56.7 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Bone Marrow (BM) Minimum Residual Disease (MRD) Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by High Baseline Bone Marrow Tumor Burden | Had BOR of CR/CRi with BM 0.01% <= MRD% < 5% | 6.7 percentage of participants |
Secondary
Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: No
BM MRD status WAS per Local Investigator and IRC assessment within 6 months after infusion pf CTL019 by baseline extramedullary disease presence of No. BM MRD were collected and measured only within responders.
Time frame: Within 6 months
Population: Efficacy Analysis Set: A subset of FAS treated with CTL019 at least 6 months prior to the clinical data cutoff. FAS: All subjects who received an infusion of CTL019. Data is based on cut-off date of 6-Oct-2017, with only 42 participants \& 40 having a BL extramedullary disease presence of No. BM MRD were collected \& measured only within responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: No | With BM MRD -ve (MRD%< 0.01%) | 62.5 percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: No | With bone marrow 0.01% <= MRD% < 5% | 5.0 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: No | With BM MRD -ve (MRD%< 0.01%) | 62.5 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: No | With bone marrow 0.01% <= MRD% < 5% | 5.0 percentage of participants |
Secondary
Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: Yes
BM MRD status was by Local Investigator and IRC assessment within 6 months after infusion pf CTL019 by baseline extramedullary disease presence of Yes. BM MRD were collected and measured only within responders.
Time frame: Within 6 months
Population: Efficacy Analysis Set: A subset of FAS treated with CTL019 at least 6 months prior to the clinical data cutoff. FAS: All subjects who received an infusion of CTL019. Data is based on cut-off date of 6-Oct-2017, with only 42 participants \& 2 having a BL extramedullary disease presence of Yes. BM MRD were collected \& measured only within responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: Yes | 100 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: Yes | 100 percentage of participants |
Secondary
Bone Marrow MRD Status Was by Flow Cytometry Within 6 Months Post CTL019 Infusion by Low Baseline Bone Marrow Tumor Burden
BM MRD status was per Local Investigator and IRC assessment within 6 months after infusion of CTL019 by low baseline bone marrow tumor burden. BM MRD were collected and measured only within responders.
Time frame: Within 6 months
Population: Efficacy Analysis Set: A subset of FAS treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on cut-off date of 6-Oct-2017, with only 42 participants and 12 having a high baseline bone marrow tumor burden. BM MRD were collected and measured only within responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Bone Marrow MRD Status Was by Flow Cytometry Within 6 Months Post CTL019 Infusion by Low Baseline Bone Marrow Tumor Burden | 83.3 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Bone Marrow MRD Status Was by Flow Cytometry Within 6 Months Post CTL019 Infusion by Low Baseline Bone Marrow Tumor Burden | 83.3 percentage of participants |
Secondary
CD19 Status of Bone Marrow/Blood Relapse in FAS Patients Who Achieved CR or CRi and Then Relapsed
The CD19 status of bone marrow/blood relapse was categorized as follows: CD19 positive, CD19 dim, CD19 negative, CD19 positive/negative & CD19 unknown
Time frame: At time of relapse up to 60 months
Population: FAS patients who achieved CR \& CRi and then relapsed. FAS: All subjects who received an infusion of CTL019
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | CD19 Status of Bone Marrow/Blood Relapse in FAS Patients Who Achieved CR or CRi and Then Relapsed | CD19 status of BM/blood relapse:positive | 22.2 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | CD19 Status of Bone Marrow/Blood Relapse in FAS Patients Who Achieved CR or CRi and Then Relapsed | CD19 status of BM/blood relapse: dim | 5.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | CD19 Status of Bone Marrow/Blood Relapse in FAS Patients Who Achieved CR or CRi and Then Relapsed | CD19 status of BM/blood relapse: negative | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | CD19 Status of Bone Marrow/Blood Relapse in FAS Patients Who Achieved CR or CRi and Then Relapsed | CD19 status of BM/blood relapse: +ve/-ve | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | CD19 Status of Bone Marrow/Blood Relapse in FAS Patients Who Achieved CR or CRi and Then Relapsed | CD19 status of BM/blood relapse: Unknown | 55.6 Percentage of participants |
Secondary
CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow
Characterize the in vivo cellular pharmacokinetic (PK) profile (levels,persistence, trafficking) of CTL019 cells in target tissues
Time frame: Enrollment; D1; D4; D7; D11; D14; D21; D28; M3; M6; M9, M12; M18; M24, M30, M36, M42, M48 for transgene levels in blood; Screening, D28, M3, M6 for transgene levels in bone marrow
Population: Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M36: blood | 10.7 copies/ug DNA | Geometric Coefficient of Variation 19.9 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Day 1 (D1): blood | 3680 copies/ug DNA | Geometric Coefficient of Variation 344.3 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D4: blood | 234 copies/ug DNA | Geometric Coefficient of Variation 197.8 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D7: blood | 4460 copies/ug DNA | Geometric Coefficient of Variation 616.2 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D11: blood | 21200 copies/ug DNA | Geometric Coefficient of Variation 262.3 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D14: blood | 12500 copies/ug DNA | Geometric Coefficient of Variation 292.1 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D21: blood | 3720 copies/ug DNA | Geometric Coefficient of Variation 480.5 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D28: blood | 1360 copies/ug DNA | Geometric Coefficient of Variation 650.3 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month 3 (M3): blood | 220 copies/ug DNA | Geometric Coefficient of Variation 224.3 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M6: blood | 146 copies/ug DNA | Geometric Coefficient of Variation 157.5 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M9: blood | 117 copies/ug DNA | Geometric Coefficient of Variation 179.3 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M12: blood | 113 copies/ug DNA | Geometric Coefficient of Variation 312.4 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M18: blood | 87.2 copies/ug DNA | Geometric Coefficient of Variation 200.3 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M24: blood | 92.7 copies/ug DNA | Geometric Coefficient of Variation 160.5 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M30: blood | 59.9 copies/ug DNA | Geometric Coefficient of Variation 150 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Enrollment blood | NA copies/ug DNA | — |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M42: blood | 35.3 copies/ug DNA | — |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M48: blood | NA copies/ug DNA | — |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Screening: Bone marrow (BM) | NA copies/ug DNA | — |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D28 BM | 646 copies/ug DNA | Geometric Coefficient of Variation 1009.7 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | M3 BM | 179 copies/ug DNA | Geometric Coefficient of Variation 182.5 |
| Tisagenlecleucel (CTL019) - All Participants | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | M6 BM | 133 copies/ug DNA | Geometric Coefficient of Variation 121.7 |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D28: blood | 2770 copies/ug DNA | Geometric Coefficient of Variation 684.8 |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month 3 (M3): blood | 690 copies/ug DNA | — |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Enrollment blood | NA copies/ug DNA | — |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Day 1 (D1): blood | 3190 copies/ug DNA | Geometric Coefficient of Variation 348.6 |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M6: blood | NA copies/ug DNA | — |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D4: blood | 48.8 copies/ug DNA | Geometric Coefficient of Variation 282.4 |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D7: blood | 231 copies/ug DNA | Geometric Coefficient of Variation 499.1 |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D28 BM | 969 copies/ug DNA | Geometric Coefficient of Variation 166.8 |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D11: blood | 423 copies/ug DNA | Geometric Coefficient of Variation 52.7 |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D14: blood | 1600 copies/ug DNA | Geometric Coefficient of Variation 337.1 |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | M6 BM | 35.3 copies/ug DNA | — |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D21: blood | 7750 copies/ug DNA | Geometric Coefficient of Variation 334.5 |
| Tisagenlecleucel (CTL019) - IRC Assessment | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Screening: Bone marrow (BM) | NA copies/ug DNA | — |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month M6: blood | 127 copies/ug DNA | — |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D28: blood | 515 copies/ug DNA | Geometric Coefficient of Variation 244650713.9 |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Screening: Bone marrow (BM) | NA copies/ug DNA | — |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D28 BM | 615 copies/ug DNA | Geometric Coefficient of Variation 4763885.9 |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Month 3 (M3): blood | 564 copies/ug DNA | — |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D7: blood | 402 copies/ug DNA | Geometric Coefficient of Variation 114.7 |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Enrollment blood | NA copies/ug DNA | — |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | M3 BM | 542 copies/ug DNA | — |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D21: blood | 1050 copies/ug DNA | Geometric Coefficient of Variation 220743.9 |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | Day 1 (D1): blood | 2440 copies/ug DNA | Geometric Coefficient of Variation 220.6 |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D14: blood | 42835.8 copies/ug DNA | Geometric Coefficient of Variation 9060 |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D11: blood | 1920 copies/ug DNA | Geometric Coefficient of Variation 8318.1 |
| Unknown | CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow | D4: blood | 88.0 copies/ug DNA | Geometric Coefficient of Variation 71 |
Secondary
Duration of Remission (DoR) Censoring Hematopoietic Stem Cell Transplantation (HSCT) by Low Baseline Bone Marrow Tumor Burden
DoR per Local Investigator & IRC assessment by low baseline marrow tumor burden
Time frame: Within 6 months
Population: EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 12 having a low baseline marrow tumor burden
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Duration of Remission (DoR) Censoring Hematopoietic Stem Cell Transplantation (HSCT) by Low Baseline Bone Marrow Tumor Burden | NA months |
| Tisagenlecleucel (CTL019) - IRC Assessment | Duration of Remission (DoR) Censoring Hematopoietic Stem Cell Transplantation (HSCT) by Low Baseline Bone Marrow Tumor Burden | NA months |
Secondary
Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: No
DoR per Local Investigator & IRC assessment by baseline extramedullary disease presence of No
Time frame: Within 6 months
Population: EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 40 having a baseline extramedullary disease presence of No
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: No | NA months |
| Tisagenlecleucel (CTL019) - IRC Assessment | Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: No | NA months |
Secondary
Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: Yes
DoR per Local Investigator & IRC assessment by baseline extramedullary disease presence of Yes.
Time frame: Within 6 months
Population: EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 2 having a baseline extramedullary disease presence of Yes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: Yes | NA months |
| Tisagenlecleucel (CTL019) - IRC Assessment | Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: Yes | NA months |
Secondary
Duration of Remission (DoR) Censoring HSCT by High Baseline Bone Marrow Tumor Burden
DoR per Local Investigator & IRC assessment by high baseline bone marrow tumor burden
Time frame: Within 6 months
Population: EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 30 having a high baseline marrow tumor burden
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Duration of Remission (DoR) Censoring HSCT by High Baseline Bone Marrow Tumor Burden | NA months |
| Tisagenlecleucel (CTL019) - IRC Assessment | Duration of Remission (DoR) Censoring HSCT by High Baseline Bone Marrow Tumor Burden | NA months |
Secondary
Duration of Remission (DOR) Per Local and IRC Assessment
DOR is the time from achievement of CR or CRi, whichever occurs first, to relapse or death due to ALL
Time frame: From CR or CRi to relapse or death up to 60 months
Population: Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Duration of Remission (DOR) Per Local and IRC Assessment | NA months |
| Tisagenlecleucel (CTL019) - IRC Assessment | Duration of Remission (DOR) Per Local and IRC Assessment | NA months |
Secondary
Event-free Survival (EFS) Per Local and IRC Assessment
EFS is the time from date of CTL019 infusion to the earliest of death, relapse or treatment failure. Treatment failure is defined as no response in the study and discontinuation from the study due to any of the following reasons: death, AE, lack of efficacy, new anticancer therapy.
Time frame: 60 Months
Population: FAS: All subjects who received an infusion of CTL019
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Event-free Survival (EFS) Per Local and IRC Assessment | 15.6 months |
| Tisagenlecleucel (CTL019) - IRC Assessment | Event-free Survival (EFS) Per Local and IRC Assessment | 15.6 months |
Secondary
Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies)
Humoral immunogenicity was measured by anti-CTL019 antibodies in human serum using a flow cytometry method. (Prevalence and incidence of immunogenicity to CTL019)
Time frame: Baseline; Day 14; Day 28; Month 3; Month 6; Month 12; Month 24, Month 36
Population: Safety set: All subjects who received an infusion of tisagenlecleucel
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Baseline: Positive | 67.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Day 14: Positive | 84.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Day 28: Positive | 80.8 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 3: Positive | 75.0 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 6: Positive | 63.5 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 12: Positive | 46.2 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 24: Positive | 11.5 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 36: Positive | 9.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Day 28: Positive | 100 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 24: Positive | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 3: Positive | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 6: Positive | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 12: Positive | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Baseline: Positive | 66.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Day 14: Positive | 100 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 36: Positive | 0 Percentage of participants |
| Unknown | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Day 28: Positive | 50.0 Percentage of participants |
| Unknown | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Day 14: Positive | 83.3 Percentage of participants |
| Unknown | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Baseline: Positive | 83.3 Percentage of participants |
| Unknown | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 3: Positive | 33.3 Percentage of participants |
| Unknown | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 24: Positive | 0 Percentage of participants |
| Unknown | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 12: Positive | 0 Percentage of participants |
| Unknown | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 6: Positive | 16.7 Percentage of participants |
| Unknown | Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies) | Month 36: Positive | 0 Percentage of participants |
Secondary
Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP)
C-Reactive Protein at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time frame: Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Population: Safety set: All subjects who received an infusion of tisagenlecleucel
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Pre-infusion | 9.21 mg/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Month 3 | 0.00 mg/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 28 | 0.00 mg/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day7 | 0.00 mg/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Baseline (BL) | 9.21 mg/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 14 | 0.00 mg/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 21 | 0.00 mg/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 21 | -0.80 mg/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 14 | 0.00 mg/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Baseline (BL) | 9.04 mg/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Pre-infusion | 8.27 mg/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 28 | -0.70 mg/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day7 | 15.00 mg/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Month 3 | -1.00 mg/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 14 | 10.50 mg/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Pre-infusion | 7.45 mg/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Baseline (BL) | 7.45 mg/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day7 | 79.55 mg/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 21 | 2.00 mg/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 28 | 1.50 mg/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Month 3 | 0.00 mg/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day7 | 108.00 mg/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 21 | -3.00 mg/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Baseline (BL) | 9.00 mg/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Month 3 | -1.00 mg/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 28 | -3.00 mg/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Pre-infusion | 9.00 mg/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 14 | 15.70 mg/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day7 | 9.10 mg/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Month 3 | -0.65 mg/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 28 | 0.00 mg/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 21 | 0.00 mg/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Baseline (BL) | 9.00 mg/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Pre-infusion | 9.00 mg/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP) | Change from BL Day 14 | 0.00 mg/L |
Secondary
Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin
Ferritin at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time frame: Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Population: Safety set: All subjects who received an infusion of tisagenlecleucel
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Pre-infusion | 1865.20 ug/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Month 3 | -124.90 ug/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 28 | 121.10 ug/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day7 | -146.50 ug/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Baseline (BL) | 1865.20 ug/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 14 | -321.30 ug/L |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 21 | 58.00 ug/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 21 | 331.00 ug/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 14 | 861.50 ug/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Baseline (BL) | 2202.22 ug/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Pre-infusion | 2202.22 ug/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 28 | 283.00 ug/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day7 | 377.80 ug/L |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Month 3 | -358.00 ug/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 14 | 10728.40 ug/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Pre-infusion | 1906.95 ug/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Baseline (BL) | 1906.95 ug/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day7 | 22735.10 ug/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 21 | 3299.85 ug/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 28 | 1104.00 ug/L |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Month 3 | -487.60 ug/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day7 | 23788.71 ug/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 21 | 3199.00 ug/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Baseline (BL) | 2078.40 ug/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Month 3 | -377.00 ug/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 28 | 1211.00 ug/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Pre-infusion | 2078.40 ug/L |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 14 | 18580.01 ug/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day7 | 358.90 ug/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Month 3 | -330.00 ug/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 28 | 280.50 ug/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 21 | 490.00 ug/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Baseline (BL) | 1983.90 ug/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Pre-infusion | 1983.90 ug/L |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin | Change from BL Day 14 | 973.00 ug/L |
Secondary
Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma
INF-gamma at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time frame: Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Population: Safety set: All subjects who received an infusion of tisagenlecleucel
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Pre-infusion | 29.63 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Month 3 | -6.08 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 28 | -6.93 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day7 | 0.47 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Baseline (BL) | 29.63 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 14 | -5.10 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 21 | -4.97 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 21 | 1.06 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 14 | -4.44 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Baseline (BL) | 22.51 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Pre-infusion | 23.39 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 28 | 0.20 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day7 | 52.59 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Month 3 | -14.58 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 14 | 58.65 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Pre-infusion | 15.73 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Baseline (BL) | 15.73 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day7 | 3023.82 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 21 | 0.53 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 28 | -1.19 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Month 3 | 21.25 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day7 | 1347.48 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 21 | 5.23 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Baseline (BL) | 4.77 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Month 3 | -0.67 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 28 | 0.36 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Pre-infusion | 5.79 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 14 | 102.04 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day7 | 72.09 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Month 3 | -5.71 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 28 | -0.62 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 21 | -0.89 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Baseline (BL) | 15.75 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Pre-infusion | 20.22 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma | Change from BL Day 14 | 1.32 pg/mL |
Secondary
Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2)
IL-2 at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time frame: Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Population: Safety set: All subjects who received an infusion of tisagenlecleucel
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Pre-infusion | 2.3 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Month 3 | NA pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 28 | NA pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day7 | 3.33 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Baseline (BL) | 2.3 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 14 | NA pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 21 | NA pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 21 | NA pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 14 | 0.00 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Baseline (BL) | 2.3 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Pre-infusion | 2.3 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 28 | NA pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day7 | 3.15 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Month 3 | NA pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 14 | NA pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Pre-infusion | 2.3 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Baseline (BL) | 2.3 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day7 | 13.14 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 21 | NA pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 28 | NA pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Month 3 | NA pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day7 | 7.48 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 21 | NA pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Baseline (BL) | 2.3 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Month 3 | NA pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 28 | NA pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Pre-infusion | 2.3 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 14 | 4.56 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day7 | 5.16 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Month 3 | NA pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 28 | NA pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 21 | NA pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Baseline (BL) | 2.3 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Pre-infusion | 2.3 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2) | Change from BL Day 14 | 0.00 pg/mL |
Secondary
Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6)
IL-6 at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time frame: Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Population: Safety set: All subjects who received an infusion of tisagenlecleucel
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Pre-infusion | 2.42 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Month 3 | 0.34 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 28 | -0.98 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day7 | -0.23 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Baseline (BL) | 2.42 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 14 | -0.36 pg/mL |
| Tisagenlecleucel (CTL019) - All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 21 | -0.97 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 21 | -0.46 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 14 | -0.67 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Baseline (BL) | 2.83 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Pre-infusion | 2.89 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 28 | -0.28 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day7 | 2.64 pg/mL |
| Tisagenlecleucel (CTL019) - IRC Assessment | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Month 3 | -0.59 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 14 | 8.88 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Pre-infusion | 1.00 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Baseline (BL) | 1.00 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day7 | 52.75 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 21 | 1.65 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 28 | 0.91 pg/mL |
| Unknown | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Month 3 | 0.56 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day7 | 141.68 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 21 | 50.75 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Baseline (BL) | 1.84 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Month 3 | 0.40 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 28 | 38.13 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Pre-infusion | 2.27 pg/mL |
| Grade 4 | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 14 | 165.16 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day7 | 2.64 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Month 3 | -0.19 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 28 | -0.03 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 21 | -0.09 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Baseline (BL) | 1.99 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Pre-infusion | 2.27 pg/mL |
| All Participants | Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6) | Change from BL Day 14 | -0.11 pg/mL |
Secondary
ORR by Baseline Extramedullary Disease Presence of No Within 6 Months Post CTL019 Infusion
ORR within 6 months after infusion of CTL019 per Local Investigator & IRC assessment by baseline extramedullary disease presence of No.
Time frame: Within 6 months
Population: EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 40 participants having no baseline extramedullary presence.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | ORR by Baseline Extramedullary Disease Presence of No Within 6 Months Post CTL019 Infusion | 67.5 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | ORR by Baseline Extramedullary Disease Presence of No Within 6 Months Post CTL019 Infusion | 67.5 percentage of participants |
Secondary
ORR by Baseline Extramedullary Disease Presence of Yes Within 6 Months Post CTL019 Infusion
ORR within 6 months after infusion of CTL019 per Local Investigator & IRC assessment by baseline extramedullary disease presence of Yes.
Time frame: Within 6 months
Population: EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 2 participants having a baseline extramedullary presence.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | ORR by Baseline Extramedullary Disease Presence of Yes Within 6 Months Post CTL019 Infusion | 100 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | ORR by Baseline Extramedullary Disease Presence of Yes Within 6 Months Post CTL019 Infusion | 100 percentage of participants |
Secondary
ORR by High Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion
ORR within 6 months after infusion of CTL019 per Local Investigator & IRC assessment by high baseline bone marrow tumor burden presence.
Time frame: Within 6 months
Population: EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 30 having a high bone marrow tumor burden at enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | ORR by High Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion | 63.3 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | ORR by High Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion | 63.3 percentage of participants |
Secondary
ORR by Low Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion
ORR within 6 months after infusion of CTL019 per Local & IRC assessment by baseline bone marrow tumor burden presence.
Time frame: Within 6 months
Population: EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 12 having a low bone marrow tumor burden at enrollment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | ORR by Low Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion | 83.3 percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | ORR by Low Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion | 83.3 percentage of participants |
Secondary
Overall Survival (OS)
OS is the time from date of CTL019 infusion to the date of death due to any reason
Time frame: 60 Months
Population: FAS: All subjects who received an infusion of CTL019
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Overall Survival (OS) | 29.9 months |
Secondary
Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC
Activation of T cells in PBMC collected from subjects in response to mCAR19 -derived peptides was used to assess the cellular immunogenicity against tisagenlecleucel. CD4 and CD8 T cell net responses (in %) were calculated for 2 non-overlapping CTL019 peptide pools (i.e., Pool 1 and Pool 2). (Lymphocyte subsets of B and T cells and description of associated safety events)
Time frame: Baseline; Day 14; Day 28; Month 3; Month 6; Month 12; Month 24, Month 36
Population: Safety set: All subjects who received an infusion of tisagenlecleucel
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 2 CD3+ CD4+ IFNg+ | 92.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 1 CD3+ CD4+ IFNg+ | 82.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 1 CD3+ CD4+ IFNg+ | 94.2 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 1 CD3+ CD4+ IFNg+ | 82.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 1 CD3+ CD4+ IFNg+ | 67.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 1 CD3+ CD4+ IFNg+ | 48.1 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 1 CD3+ CD4+ IFNg+ | 17.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 1 CD3+ CD4+ IFNg+ | 9.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 1 CD3+ CD4+ IFNg+ | 92.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 2 CD3+ CD4+ IFNg+ | 82.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 2 CD3+ CD4+ IFNg+ ) | 94.2 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 2 CD3+ CD4+ IFNg+ | 82.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 2 CD3+ CD4+ IFNg+ | 67.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 2 CD3+ CD4+ IFNg+ | 48.1 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 2 CD3+ CD4+ IFNg+ | 17.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 2 CD3+ CD4+ IFNg+ | 9.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 1 CD3+ CD8+ IFNg+ | 92.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 1 CD3+ CD8+ IFNg+ | 82.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 1 CD3+ CD8+ IFNg+ | 94.2 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 1 CD3+ CD8+ IFNg+ | 82.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 1 CD3+ CD8+ IFNg+ | 67.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 1 CD3+ CD8+ IFNg+ | 48.1 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 1 CD3+ CD8+ IFNg+ | 17.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 1 CD3+ CD8+ IFNg+ | 9.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 2 CD3+ CD8+ IFNg+ | 92.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 2 CD3+ CD8+ IFNg+ | 82.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 2 CD3+ CD8+ IFNg+ | 94.2 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 2 CD3+ CD8+ IFNg+ | 82.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 2 CD3+ CD8+ IFNg+ | 67.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 2 CD3+ CD8+ IFNg+ | 48.1 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 2 CD3+ CD8+ IFNg+ | 17.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 2 CD3+ CD8+ IFNg+ | 9.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 1 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 1 CD3+ CD4+ IFNg+ | 83.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 2 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 1 CD3+ CD8+ IFNg+ | 83.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 1 CD3+ CD4+ IFNg+ | 100 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 2 CD3+ CD4+ IFNg+ | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 2 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 1 CD3+ CD4+ IFNg+ | 100 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 1 CD3+ CD8+ IFNg+ | 100 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 1 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 1 CD3+ CD4+ IFNg+ | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 2 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 2 CD3+ CD8+ IFNg+ | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 1 CD3+ CD4+ IFNg+ | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 1 CD3+ CD8+ IFNg+ | 100 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 2 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 1 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 2 CD3+ CD4+ IFNg+ | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 1 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 1 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 1 CD3+ CD8+ IFNg+ | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 2 CD3+ CD8+ IFNg+ | 100 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 1 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 2 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 2 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 2 CD3+ CD4+ IFNg+ | 83.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 1 CD3+ CD8+ IFNg+ | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 2 CD3+ CD8+ IFNg+ | 83.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 2 CD3+ CD4+ IFNg+ | 100 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 2 CD3+ CD8+ IFNg+ | 100 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 2 CD3+ CD8+ IFNg+ | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 2 CD3+ CD4+ IFNg+ ) | 100 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 1 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 2 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 2 CD3+ CD4+ IFNg+ | 33.3 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 2 CD3+ CD4+ IFNg+ | 16.7 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 2 CD3+ CD8+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 2 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 2 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 2 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 2 CD3+ CD8+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 1 CD3+ CD8+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 1 CD3+ CD8+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 1 CD3+ CD8+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 2 CD3+ CD8+ IFNg+ | 33.3 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 1 CD3+ CD8+ IFNg+ | 33.3 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 2 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 1 CD3+ CD8+ IFNg+ | 16.7 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 1 CD3+ CD4+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 1 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 1 CD3+ CD4+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 2 CD3+ CD8+ IFNg+ | 16.7 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 1 CD3+ CD4+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 3: Pool 1 CD3+ CD4+ IFNg+ | 33.3 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 1 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 6: Pool 1 CD3+ CD4+ IFNg+ | 57.8 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 2 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 12: Pool 1 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 24: Pool 1 CD3+ CD4+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Month 36: Pool 1 CD3+ CD8+ IFNg+ | 0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 28: Pool 2 CD3+ CD4+ IFNg+ ) | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 2 CD3+ CD4+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Day 14: Pool 2 CD3+ CD4+ IFNg+ | 50.0 Percentage of participants |
| Unknown | Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC | Baseline: Pool 2 CD3+ CD8+ IFNg+ | 50.0 Percentage of participants |
Secondary
Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment
The levels (%) of CD19+ total B cells amongst viable white blood cells (WBC) in peripheral blood
Time frame: Enrollment/Pre-Chemotherapy; Pre-infusion; Baseline; Day 7; Day 14; Day 21; Day 28; Month 3; Month 6; Month 9; Month 12; Month 24; Month 36
Population: Safety set: All subjects who received an infusion of tisagenlecleucel
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Enrollment/Pre-Chemotherapy | 26.8 Percentage of CD19+ B cell levels | Standard Deviation 28.733 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Pre-infusion | 0.02 Percentage of CD19+ B cell levels | — |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Baseline | 25.11 Percentage of CD19+ B cell levels | Standard Deviation 28.584 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 7 | 1.06 Percentage of CD19+ B cell levels | Standard Deviation 3.735 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 14 | 0.73 Percentage of CD19+ B cell levels | Standard Deviation 5.096 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 21 | 0.01 Percentage of CD19+ B cell levels | Standard Deviation 0.017 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 28 | 0.02 Percentage of CD19+ B cell levels | Standard Deviation 0.069 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 3 | 0.79 Percentage of CD19+ B cell levels | Standard Deviation 1.971 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 6 | 1.86 Percentage of CD19+ B cell levels | Standard Deviation 7.958 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 9 | 0.63 Percentage of CD19+ B cell levels | Standard Deviation 2.18 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 12 | 0.85 Percentage of CD19+ B cell levels | Standard Deviation 2.42 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 24 | 1.74 Percentage of CD19+ B cell levels | Standard Deviation 3.446 |
| Tisagenlecleucel (CTL019) - All Participants | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 36 | 1.10 Percentage of CD19+ B cell levels | Standard Deviation 2.106 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 21 | 19.67 Percentage of CD19+ B cell levels | Standard Deviation 32.553 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Baseline | 52.29 Percentage of CD19+ B cell levels | Standard Deviation 36.758 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 28 | 34.97 Percentage of CD19+ B cell levels | Standard Deviation 36.648 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 6 | 9.70 Percentage of CD19+ B cell levels | — |
| Tisagenlecleucel (CTL019) - IRC Assessment | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 7 | 34.40 Percentage of CD19+ B cell levels | Standard Deviation 46.922 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Enrollment/Pre-Chemotherapy | 52.29 Percentage of CD19+ B cell levels | Standard Deviation 36.758 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 3 | 0.57 Percentage of CD19+ B cell levels | — |
| Tisagenlecleucel (CTL019) - IRC Assessment | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 14 | 33.76 Percentage of CD19+ B cell levels | Standard Deviation 45.359 |
| Unknown | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 7 | 23.18 Percentage of CD19+ B cell levels | Standard Deviation 38.772 |
| Unknown | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Pre-infusion | 46.80 Percentage of CD19+ B cell levels | — |
| Unknown | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 3 | 11.26 Percentage of CD19+ B cell levels | Standard Deviation 15.917 |
| Unknown | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 21 | 16.13 Percentage of CD19+ B cell levels | Standard Deviation 35.929 |
| Unknown | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Month 6 | 0.01 Percentage of CD19+ B cell levels | — |
| Unknown | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Enrollment/Pre-Chemotherapy | 32.66 Percentage of CD19+ B cell levels | Standard Deviation 28.102 |
| Unknown | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 14 | 3.43 Percentage of CD19+ B cell levels | Standard Deviation 7.52 |
| Unknown | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Day 28 | 0.02 Percentage of CD19+ B cell levels | Standard Deviation 0.012 |
| Unknown | Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment | Baseline | 29.50 Percentage of CD19+ B cell levels | Standard Deviation 24.466 |
Secondary
Percentage of Participants With Clinical Response Without Stem Cell Transplantation (SCT) at Month 6 - Per IRC Assessment
Evaluate the percentage of participants who achieved CR or CRi at Month 6 without SCT between tisagenlecleucel infusion and Month 6 response assessment.
Time frame: Month 6
Population: Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Percentage of Participants With Clinical Response Without Stem Cell Transplantation (SCT) at Month 6 - Per IRC Assessment | 53.1 Percentage of participants |
Secondary
Percentage of Participants With CR or CRi With Minimum Residual Disease (MRD) Negative Bone Marrow 6 Months After CTL019 Infusion
Percentage of participants with best overall response (BOR) of CR or CRi with MRD negative bone marrow status 6 months after CTL019 infusion among all participants who achieved CR or CRi per Local Investigator & IRC assessment
Time frame: within 6 months
Population: Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Percentage of Participants With CR or CRi With Minimum Residual Disease (MRD) Negative Bone Marrow 6 Months After CTL019 Infusion | 67.2 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Percentage of Participants With CR or CRi With Minimum Residual Disease (MRD) Negative Bone Marrow 6 Months After CTL019 Infusion | 67.2 Percentage of participants |
Secondary
Percentage of Subjects Who Achieved CR or CRi and Then Proceeded to SCT While in Remission Prior to Month 6 Response - Per IRC Assessment
Evaluate the percentage of subjects who achieved CR or CRi and then proceeded to SCT while in remission prior to Month 6 response assessment.
Time frame: prior to Month 6
Population: Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Percentage of Subjects Who Achieved CR or CRi and Then Proceeded to SCT While in Remission Prior to Month 6 Response - Per IRC Assessment | 7.8 Percentage of participants |
Secondary
Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: AUC0-28d and AUC0-84d
Characterize the in vivo cellular pharmacokinetic (PK) profile. AUC0-28d and AUC0-84d is defined as the AUC from time zero to day 28 and 84 or other disease assessment days, in peripheral blood (% or copies/μg x days). Data was only reported for evaluable PK parameters. The Overall Number of Participants Analyzed represents all participants for which a baseline assessment was collected for this Outcome Measure, and therefore these participants did contribute data to this estimation parameter, whereas the Number Analyzed per Row represents the number of participants with data available at either 28 or 84 days.
Time frame: 0 - 28 days post-infusion for AUC0-28d and 0 - 84 days post-infusion for AUC0-84d
Population: Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: AUC0-28d and AUC0-84d | AUC0-28d | 261000 copies/µg*days | Geometric Coefficient of Variation 199.8 |
| Tisagenlecleucel (CTL019) - All Participants | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: AUC0-28d and AUC0-84d | AUC0-84d | 368000 copies/µg*days | Geometric Coefficient of Variation 182.9 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: AUC0-28d and AUC0-84d | AUC0-28d | 151000 copies/µg*days | Geometric Coefficient of Variation 71.7 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: AUC0-28d and AUC0-84d | AUC0-84d | 443000 copies/µg*days | Geometric Coefficient of Variation 79.9 |
| Unknown | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: AUC0-28d and AUC0-84d | AUC0-28d | 617000 copies/µg*days | — |
| Unknown | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: AUC0-28d and AUC0-84d | AUC0-84d | 1340000 copies/µg*days | — |
Secondary
Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Clast
Characterize the in vivo cellular pharmacokinetic (PK) profile. Clast is defined as the last observed quantifiable concentration in peripheral blood (% or copies/ug)
Time frame: Day 28
Population: Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Clast | 223 copies/µg | Geometric Coefficient of Variation 283.4 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Clast | 1980 copies/µg | Geometric Coefficient of Variation 207.5 |
| Unknown | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Clast | 80.3 copies/µg | — |
Secondary
Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Cmax
Characterize the in vivo cellular pharmacokinetic (PK) profile. Cmax is defined as the maximum (peak) observed in peripheral blood drug concentration after single dose administration (% or copies/μg).
Time frame: Day 28
Population: Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Cmax | 28300 copies/µg | Geometric Coefficient of Variation 197 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Cmax | 15100 copies/µg | Geometric Coefficient of Variation 49.4 |
| Unknown | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Cmax | 52500 copies/µg | Geometric Coefficient of Variation 91.1 |
Secondary
Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: T1/2
Characterize the in vivo cellular pharmacokinetic (PK) profile. T1/2 is defined as the half-life associated with the disposition phase slopes (alpha, beta, gamma etc.) of a semi logarithmic concentration-time curve (days) in peripheral blood
Time frame: Day 28
Population: Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: T1/2 | 31.9 days | Geometric Coefficient of Variation 415.1 |
| Tisagenlecleucel (CTL019) - IRC Assessment | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: T1/2 | 4.36 days | Geometric Coefficient of Variation 421.2 |
| Unknown | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: T1/2 | 42.1 days | — |
Secondary
Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tlast
Characterize the in vivo cellular pharmacokinetic (PK) profile. Tlast is defined as the time of last observed quantifiable concentration in peripheral blood (days)
Time frame: Day 28
Population: Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tlast | 179 days |
| Tisagenlecleucel (CTL019) - IRC Assessment | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tlast | 26.9 days |
| Unknown | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tlast | 210 days |
Secondary
Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tmax
Characterize the in vivo cellular pharmacokinetic (PK) profile. Tmax is defined as the time to reach maximum (peak) peripheral blood drug concentration after single dose administration (days)
Time frame: Day 28
Population: Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tmax | 9.84 days |
| Tisagenlecleucel (CTL019) - IRC Assessment | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tmax | 20.0 days |
| Unknown | Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tmax | 11.9 days |
Secondary
Relapse-free Survival (RFS) for Responders Per Local and IRC Assessment
RFS is the time from achievement of CR or CRi whichever occurs first to relapse or death due to any cause during CR or CRi.
Time frame: 60 Months
Population: Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Relapse-free Survival (RFS) for Responders Per Local and IRC Assessment | NA months |
| Tisagenlecleucel (CTL019) - IRC Assessment | Relapse-free Survival (RFS) for Responders Per Local and IRC Assessment | NA months |
Secondary
Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion
Percentage of participants attaining CR or CRi with MRD negative bone marrow status at Day 28 +/- 4 days after CTL019 infusion per Local Investigator and IRC assessment. BM MRD were only collected and measured only within responders.
Time frame: Day 28
Population: Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS. BM MRD were only collected and measured only within responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion | With BM MRD -ve: i.e. MRD% < 0.01% | 71.9 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion | With BM 0.01% <= MRD% < 5% | 1.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion | With BM MRD% >= 5% | 1.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion | BM MRD not available | 6.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion | BM MRD not available | 6.3 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion | With BM MRD -ve: i.e. MRD% < 0.01% | 71.9 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion | With BM MRD% >= 5% | 1.6 Percentage of participants |
| Tisagenlecleucel (CTL019) - IRC Assessment | Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion | With BM 0.01% <= MRD% < 5% | 1.6 Percentage of participants |
Secondary
Site of Initial Relapse Among FAS Patients Who Achieved CR/CRi and Then Relapsed
This is the site of involvement of initial relapse after achieving a best overall response of CR/CRi.
Time frame: At time of relapse up to 60 months
Population: FAS patients who achieved CR \& CRi and then relapsed. FAS: All subjects who received an infusion of CTL019
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Site of Initial Relapse Among FAS Patients Who Achieved CR/CRi and Then Relapsed | Unknown | 16.7 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Site of Initial Relapse Among FAS Patients Who Achieved CR/CRi and Then Relapsed | BM/blood relapse | 72.2 Percentage of participants |
| Tisagenlecleucel (CTL019) - All Participants | Site of Initial Relapse Among FAS Patients Who Achieved CR/CRi and Then Relapsed | Extramedullary only | 27.8 Percentage of participants |
Secondary
Time to B-cell Recovery in Participants Who Achieved CR or CRi by IRC
Time to B cell recovery was defined as the time from onset of remission to the earliest time when the percentage of CD19+ total B cell among viable WBC is ≥ 1% or among lymphocyte is at least 3%.
Time frame: during the whole study, up to 60 months
Population: FAS patients who achieved CR or CRi. FAS: All subjects who received an infusion of CTL019
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisagenlecleucel (CTL019) - All Participants | Time to B-cell Recovery in Participants Who Achieved CR or CRi by IRC | 35.5 Months |