B-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
Pediatric, ALL, Cell therapy, Lymphoblastic Leukemia, Acute, High Risk, Childhood, CTL019, tisagenlecleucel, Pediatric patients, r/r B-cell ALL, high risk B-cell ALL at first relapse, high risk B-cell ALL that relapsed < 6 months post allo-HSCT
Brief summary
This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL.
Detailed description
This was a initially a one cohort, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL. This main cohort completed enrollment. Two new cohorts were added via an amendment, Cohort 1 for high risk B-cell ALL patients at first relapse, and Cohort 2 for feasibility and safety of CTL019 in high risk B-cell ALL in patients that relapsed \<6 months post allo-HSCT. Due to lack of recruitment, Cohort 1 and Cohort 2 halted recruitment. This decision was not related to any safety issue. The study had the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation & Lymphodepleting Chemotherapy), Treatment and Primary Follow-up, Secondary Follow-up (if applicable) and Survival Follow-up. The total duration of the study is 5 years from CTL019 cell infusion. Efficacy analyses were performed only on the Main Cohort (n=79) who were infused with tisagenlecleucel. However, the data on disposition and demographics presented in this section includes all patients enrolled to the study (98) and all infused patients (80) (Main Cohort + Cohort 1). No patients were enrolled in Cohort 2.
Interventions
BIOLOGICALCTL019
Tisagenlecleucel was administered as a single iv infusion. Dose: 2.0 to 5.0x10\^6 tisagenlecleucel per kg body weight (for patients ≤ 50 kg) or 1.0 to 2.5x10\^8 tisagenlecleucel (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
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Relapsed or refractory pediatric B-cell ALL 2. Adequate organ function 3. For relapsed patients, documentation of CD19 tumor expression within 3 months of study entry. 4. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening. 5. Life expectancy \> 12 weeks. 6. Karnofsky (age ≥16 years) or Lansky (age \< 16 years) performance status ≥ 50 at screening 7. Signed written informed consent and assent forms 8. Must meet the institutional criteria to undergo leukapheresis or have an acceptable, store leukapheresis product 9. Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site. 10. Cohort 1 only: 1. First relapse AND hypodiploid cytogenetics OR 2. First relapse AND t(17;19) with defined TCF3-HLF fusion OR 3. First relapse with any cytogenetics provided the relapse occurred ≤ 36 months of initial diagnosis AND MRD at end of reinduction therapy is ≥0.01% by flow cytometry (local assessment)
Exclusion criteria
1. Isolated extra-medullary disease relapse 2. 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. 3. Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell \[sIg positive and kappa or lambda restricted positivity\] ALL, with FAB L3 morphology and /or a MYC translocation) 4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease 5. Treatment with any prior gene therapy product 6. Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy 7. Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening 8. Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening 9. Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). 10. Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines. 11. Patient has an investigational medicinal product within the last 30 days prior to screening. 12. Pregnant or nursing (lactating) women. 13. Women of child-bearing potential, defined as physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception for at least 12 months after the CTL019 infusion and after CAR T-cells are no longer present by qPCR on two consecutive tests 14. Sexually active males must use a condom during intercourse at least 12 months after the CTL019 infusion after CAR T-cells are no longer present by qPCR on two consecutive tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Remission Rate (ORR) as Determined by Independent Review Committee (IRC) Assessment. | during the 3 months after tisagenlecleucel administration | Evaluating the efficacy of tisagenlecleucel therapy from all manufacturing facilities as measured by overall remission rate (ORR) during the 3 months after tisagenlecleucel administration. ORR included complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by an Independent Review Committee assessment. Per response criteria defined by National Comprehensive Cancer Network (NCCN), American Society of Hematology (ASH) and International Working Group (IWG) guidelines. CR is defined as: Bone marrow \<5% blasts, Peripheral blood: Neutrophils \>1.0 x 10\^9/L, and Platelets \>100 x 10\^9/L and Circulating blasts \<1% and No evidence of extramedullary disease, at least 7 days transfusion independency. CRi is defined as all the prior criteria being met, except that the following exists: Neutrophils ≤1.0 x 10\^9/L, and/or Platelets ≤100 x 10\^9/L, and/or Platelet and/or neutrophil transfusions ≤7 days before the date of the peripheral blood sample for disease assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From US Manufacturing Facility as Per IRC in the Main Cohort Only (Key Secondary) | 3 months after tisagenlecleucel administration | These are the percentage of participants who achieved Best Overall Response (BOR) of complete response (CR) or complete response with incomplete blood count recovery (CRi) with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from US manufacturing facilities only, by IRC assessment. |
| Percentage of Participants With Best Overall Response (BOR) of CR or CRi With MRD Negative Bone Marrow by Flow Cytometry From All Manufacturing Facilities as Per IRC in the Main Cohort Only (Key Secondary) | 3 months after tisagenlecleucel administration | These are the percentage of participants who achieved Best Overall Response (BOR) of CR or CRi with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from all manufacturing facilities by IRC assessment. MRD negative = MRD% \< 0.01% |
| Percentage of Participants Who Achieved CR or CRi Without Hematopoietic Stem Cell Transplantation (HSCT) | 6 months after tisagenlecleucel administration | These are the participants who achieved CR or CRi without HSCT between tisagenlecleucel (CTL019) infusion and Month 6 response assessment. |
| Percentage of Participants Who Achieved CR or CRi and Then Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) While in Remission Prior to Month 6 Resoonse | 6 months | These are the participants who achieved CR or CRi and then proceeded to HSCT while in remission prior to Month 6 response assessment |
| Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) After Tisagenlecleucel (CTL019) Infusion | up to 6 months | These are the participants who achieved CR or CRi and then proceeded to SCT after being infused by tisagenlecleucel. |
| Duration of Remission (DOR) | 60 months | DOR is the time from achievement of CR or CRi at any time post-infusion, whichever occurs first, to relapse or death. |
| Site of Involvement of Subsequent Relapse | 60 months | Anatomical location of relapse in participants who achieved prior CR/CRi subsequent to tisagenlecleucel infusion. |
| Relapse-free Survival Per IRC Assessment | 60 months | RFS is the time from achievement of CR or CRi at any time post-infusion, whichever occurs first, to relapse or death due to any cause during CR or CRi. |
| Event-free Survival Per IRC Assessment | 60 months | EFS is the time from date of tisagenlecleucel infusion to the earliest of death, relapse or treatment failure. |
| Overall Survival (OS) | 60 months | OS, is the time from date of tisagenlecleucel infusion to the date of death due to any reason. |
| Percentage of Participants Attaining CR or CRi at Day 28 +/- 4 Days Post Tisagenlecleucel (CTL019) Infusion by IRC Assessment | 1 month | These are participants who had a day 28 response (CR or CRi response) by IRC assessment. |
| Response as a Function of Baseline Tumor Burden (Tumor Load) in Main Cohort Only | 3 months | Percentage of participants who achieved BOR of CR or CRi by flow cytometry as a function of baseline bone marrow tumor burden. |
| Bone Marrow MRD Status by Flow Cytometry Per IRC Assessment | 28 days | Percentage of participants who achieved CR or CRi response with bone marrow MRD negative (MRD \< 0.01%) after tisagenlecleucel infusion by flow cytometry. |
| Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood by Day 28 Response by Independent Review Committee (IRC) Assessment | Month 60 | This is the summary of cellular kinetic concentrations for Tisagenlecleucel (CTL019) transgene levels by qPCR in peripheral blood. |
| Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow by Day 28 Response by IRC Assessment | Month 6 | This is the summary of cellular kinetic concentrations for Tisagenlecleucel (CTL019) transgene levels by qPCR in bone marrow. |
| Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Peripheral Blood by Day 28 Disease Response Per IRC Assessment | Month 60 | This is the summary cellular kinetic concentrations for CTL019 by flow cytometry in peripheral blood. It evaluated the persistence of transduced CTL019 cells post-infusion. Observation was up to Month 60 for peripheral blood. |
| Percentage of Participants With Overall Remission Rate (ORR) as Per IRC From US Manufacturing Facilities in the Main Cohort Only (Key Secondary) | 3 months after tisagenlecleucel administration | These are the percentage of participants with ORR who achieved overall remission rate which includes complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by IRC assessment after having been infused with tisagenlecleucel from US manufacturing facilities. |
| Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | 60 months | Cmax is the maximum (peak) observed in peripheral blood drug concentration after single dose administration reported by CR/CRi, no response (NR), Unknown and by All participants. D28 refers to the timepoint for definition of responder populations, whereas M60 is the actual timepoint for endpoint assessment. The reported Cmax is the summary of maximum level observed based on the data from each patient and based on all the data that's been collected for up to 60 months in a patient. |
| Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | 60 months | Tmax is the time to reach maximum (peak) peripheral blood drug concentration after single dose administration (days), reported by CR/CRi, no response (NR), Unknown and by All participants. D28 refers to the timepoint for definition of responder populations, whereas M60 is the actual timepoint for endpoint assessment. The time frame of 60 months refers to the duration for which the data were reviewed to identify the time of Cmax for this measure. |
| Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | 0 to 84 days after infusion | AUC (area under curve) from day of infusion to day 28 or other disease assessment days, in peripheral blood (% or copies/μg x days), reported by CR/CRi, no response (NR), Unknown and by All participants. D28 refers to the timepoint for definition of responder populations, whereas 84 days is the actual timepoint for endpoint assessment. : AUC is defined based on the time window i.e., AUC from 0 to 84 days after infusion. Therefore, the time frame specifies the maximum time for up to which the data are used for estimation of AUC (84 days for AUC84d). |
| Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC | 60 months | Persistence is defined as the time corresponding to last quantifiable transgene level in peripheral blood (Tlast), reported by CR/CRi, no response (NR), Unknown and by All participants. D28 refers to the timepoint for definition of responder populations, whereas M60 is the actual timepoint for endpoint assessment. |
| Prevalence and Incidence of Immunogenicity to Tisagenlecleucel (CTL019) | At any time post-baseline, up to a max. of 60 months | This is defined as the percentage of participants who tested positive for anti-mCAR19 antibodies at any time post-baseline, reported by CR/CRi, no response (NR), Unknown and by All participants. . |
| Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | Month 3, M6, M12, M24, M60 | The PedsQL questionnaire was for patients ≥ 8-years-old who achieved BOR as CR or CRi within 3 months and the questionnaire was on emotional, social, school, physical, and psychosocial health. Scores are transformed on a scale from 0 to 100, with the sum of all the items over the number of items answered on all the scales. The total scale score is the averaged value of scores of subscales, which means for each subscale and the total scale, the allowed ranges are 0-100. Higher scores on the PedsQL questionnaire for these subscales indicate consistent improvement of health-related quality of life (HRQol). |
| Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | Month 60 | Results from the EQ-5D questionnaire is for number of participants who achieved CR or CRi at month 60. The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain & discomfort, anxiety & depression. Respondents are asked to choose the statement in each dimension that best describes their health status on the day surveyed. Their responses are coded as a number (1, 2, or 3) that corresponds to the respective level of severity: 1 indicates no problems, 2 some problems, and 3 severe problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that describes the patient's health state. The scores are then normalized to a value from 0-100 where higher scores = better HRQOL & fewer problems or symptoms. |
| Develop a Score Utilizing Clinical and Biomarker Data and Assess Its Ability for Early Prediction of Cytokine Release Syndrome (CRS) | 3 months | Derivation of a score to predict cytokine release syndrome. Considering the complexity and challenges of building a scoring system based on limited data from the trial, this analysis was not performed. |
| Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (C Reactive Protein & Ferritin) | Maximum post-baseline (approx. 60 months) | Profile of soluble immune factors of key inflammatory markers and cytokine parameters in blood by maximum CRS grade that may be key to cytokine release syndrome (CRS). |
| Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Maximum post-baseline (approx. 60 months) | Profile of soluble immune factors of key inflammatory markers and cytokine parameters in blood by maximum CRS grade that may be key to cytokine release syndrome (CRS). |
| Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | Month 3, Month 12, Maximum post-baseline (approx. 60 months) | Levels of B and T cells (blood and bone marrow) prior to and following CTL019 infusion for safety monitoring |
| Percentage of Participants With Overall Remission Rate (ORR) - From Fraunhofer Institute Manufacturing Facility | 60 months | These are the percentage of participants with ORR who achieved overall remission rate which includes complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by IRC assessment after having been infused with tisagenlecleucel from Fraunhofer Institute manufacturing facility. |
| Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From Fraunhofer Institute Manufacturing Facility as Per IRC | 3 months | These are the percentage of participants who achieved Best Overall Response (BOR) of CR or CRi with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from Fraunhofer Institute manufacturing facilities only, by IRC assessment. |
| Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood - Tisagenlecleucel Manufactured From Fraunhofer Institute | Month 60 | This is the summary of cellular kinetic concentrations for Tisagenlecleucel (CTL019) transgene levels by qPCR, by disease response in blood by IRC assessment. The assessment of the efficacy, safety and in vivo cellular pharmacokinetics are for patients infused with tisagenlecleucel manufactured by Fraunhofer Institute. |
| Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow - Tisagenlecleucel Manufactured From Fraunhofer Institute | Month 3 | This is the summary of cellular kinetic concentrations for Tisagenlecleucel (CTL019) transgene levels by qPCR, by disease response in bone marrow by IRC assessment. The assessment of the efficacy, safety and in vivo cellular pharmacokinetics are for patients infused with tisagenlecleucel manufactured by Fraunhofer Institute. |
| Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Bone Marrow by Day 28 Response by IRC Assessment | Month 6 | This is the summary cellular kinetic concentrations for CTL019 by flow cytometry. It evaluated the persistence of transduced CTL019 cells post-infusion. Observation was up to Month 6 for bone marrow. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Japan, Norway, Spain, United States
Participant flow
Recruitment details
98 patients met the eligibility criteria and apheresis was accepted by the manufacturing facility, 80 patients were infused in this study: 79 in the Main Cohort and 1 in Cohort 1. No patients were infused in Cohort 2. Patients could discontinue the trial after meeting the eligibility criteria and prior to tisagenlecleucel infusion.
Pre-assignment details
This study was conducted in 11 countries with 23 sites.
Participants by arm
| Arm | Count |
|---|---|
| Main Cohort: Single Dose of CTL019 Pediatric patients with relapsed or refractory B-cell ALL who were treated with single dose of tisagenlecleucel (CTL019). | 79 |
| Cohort 1: Single Dose of CTL019 Pediatric B-ALL patients who are very high risk at first relapse. | 1 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 23 | 0 |
| Overall Study | Lack of Efficacy | 10 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | New therapy for study indication | 8 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Subject/guardian decision | 5 | 1 |
Baseline characteristics
| Characteristic | Main Cohort: Single Dose of CTL019 | Cohort 1: Single Dose of CTL019 | Total |
|---|---|---|---|
| Age, Continuous | 12 Years STANDARD_DEVIATION 5.38 | 4 Years | 11.9 Years STANDARD_DEVIATION 5.42 |
| Race/Ethnicity, Customized Asian | 10 Participants | 0 Participants | 10 Participants |
| Race/Ethnicity, Customized Other | 11 Participants | 0 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 58 Participants | 1 Participants | 59 Participants |
| Sex: Female, Male Female | 34 Participants | 0 Participants | 34 Participants |
| Sex: Female, Male Male | 45 Participants | 1 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 33 / 79 | 0 / 1 |
| other Total, other adverse events | 79 / 79 | 1 / 1 |
| serious Total, serious adverse events | 63 / 79 | 0 / 1 |
Outcome results
Primary
Percentage of Participants With Overall Remission Rate (ORR) as Determined by Independent Review Committee (IRC) Assessment.
Evaluating the efficacy of tisagenlecleucel therapy from all manufacturing facilities as measured by overall remission rate (ORR) during the 3 months after tisagenlecleucel administration. ORR included complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by an Independent Review Committee assessment. Per response criteria defined by National Comprehensive Cancer Network (NCCN), American Society of Hematology (ASH) and International Working Group (IWG) guidelines. CR is defined as: Bone marrow \<5% blasts, Peripheral blood: Neutrophils \>1.0 x 10\^9/L, and Platelets \>100 x 10\^9/L and Circulating blasts \<1% and No evidence of extramedullary disease, at least 7 days transfusion independency. CRi is defined as all the prior criteria being met, except that the following exists: Neutrophils ≤1.0 x 10\^9/L, and/or Platelets ≤100 x 10\^9/L, and/or Platelet and/or neutrophil transfusions ≤7 days before the date of the peripheral blood sample for disease assessment.
Time frame: during the 3 months after tisagenlecleucel administration
Population: Full Analysis Set (FAS): The Full analysis set comprised all patients who received infusion of tisagenlecleucel in the Main Cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage of Participants With Overall Remission Rate (ORR) as Determined by Independent Review Committee (IRC) Assessment. | 82.3 Percentage of participants |
| Cohort 1: Single Dose of CTL019 | Percentage of Participants With Overall Remission Rate (ORR) as Determined by Independent Review Committee (IRC) Assessment. | 100.0 Percentage of participants |
p-value: <0.0001Clopper-Pearson
Secondary
Bone Marrow MRD Status by Flow Cytometry Per IRC Assessment
Percentage of participants who achieved CR or CRi response with bone marrow MRD negative (MRD \< 0.01%) after tisagenlecleucel infusion by flow cytometry.
Time frame: 28 days
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Bone Marrow MRD Status by Flow Cytometry Per IRC Assessment | 75.9 Percentage of participants |
| Cohort 1: Single Dose of CTL019 | Bone Marrow MRD Status by Flow Cytometry Per IRC Assessment | 100.0 Percentage of participants |
Secondary
Develop a Score Utilizing Clinical and Biomarker Data and Assess Its Ability for Early Prediction of Cytokine Release Syndrome (CRS)
Derivation of a score to predict cytokine release syndrome. Considering the complexity and challenges of building a scoring system based on limited data from the trial, this analysis was not performed.
Time frame: 3 months
Population: This objective was not associated with any data collection from participants. The original plan was to mathematically derive a score from other endpoints measures (e.g., a score combing age, value of CRP, Ferritin, Interferon gamma, etc.). Those potential biomarkers were used to derive the scores that are already reported in other tables. None of the biomarkers analyzed proved to be prognostic for the onset or severity of CRS, hence finally no score was derived and no data for this objective.
Secondary
Duration of Remission (DOR)
DOR is the time from achievement of CR or CRi at any time post-infusion, whichever occurs first, to relapse or death.
Time frame: 60 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel and who achieved CR or CRi.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Duration of Remission (DOR) | 46.8 months |
| Cohort 1: Single Dose of CTL019 | Duration of Remission (DOR) | NA months |
Secondary
Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire
Results from the EQ-5D questionnaire is for number of participants who achieved CR or CRi at month 60. The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain & discomfort, anxiety & depression. Respondents are asked to choose the statement in each dimension that best describes their health status on the day surveyed. Their responses are coded as a number (1, 2, or 3) that corresponds to the respective level of severity: 1 indicates no problems, 2 some problems, and 3 severe problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that describes the patient's health state. The scores are then normalized to a value from 0-100 where higher scores = better HRQOL & fewer problems or symptoms.
Time frame: Month 60
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel and who had evaluable results at the measured time points. This analysis included a subset of FAS who had any data of the particular questionnaire at the measured timepoints. Therefore, no participants in Cohort 1 had questionnaire data for tisagenlecleucel at the measured time points, so no data was collected for Cohort 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Mobility - No problems | 15 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Mobility - Some problems | 1 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Mobility - Severe problems | 0 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Self-care - No problems | 16 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Self-care - Some problems | 0 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Self-care - Severe problems | 0 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Usual activities - No problems | 15 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Usual activities - Some problems | 0 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Usual activities - Severe problems | 1 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Pain/discomfort - No problems | 14 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Pain/discomfort - Some problems | 2 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Pain/discomfort - Severe problems | 0 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Anxiety/depression - No problems | 12 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Anxiety/depression - Some problems | 4 Participants |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire | M60: Anxiety/depression - Severe problems | 0 Participants |
Secondary
Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire
The PedsQL questionnaire was for patients ≥ 8-years-old who achieved BOR as CR or CRi within 3 months and the questionnaire was on emotional, social, school, physical, and psychosocial health. Scores are transformed on a scale from 0 to 100, with the sum of all the items over the number of items answered on all the scales. The total scale score is the averaged value of scores of subscales, which means for each subscale and the total scale, the allowed ranges are 0-100. Higher scores on the PedsQL questionnaire for these subscales indicate consistent improvement of health-related quality of life (HRQol).
Time frame: Month 3, M6, M12, M24, M60
Population: FAS: the Full analysis set comprised all patients who received infusion of tisagenlecleucel and who had evaluable results at the measured time points. This analysis included a subset of FAS who had any data of the particular questionnaire at the specific timepoint. Therefore, no participants in Cohort 1 had questionnaire data for tisagenlecleucel at the measured time points, so no data was collected for Cohort 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M3 change from baseline - Emotional | 14.5 Scores on a scale | Standard Error 17.98 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M6 change from baseline - Emotional | 15.9 Scores on a scale | Standard Error 18.96 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M12 change from baseline - Emotional | 24.6 Scores on a scale | Standard Error 23.74 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M24 change from baseline - Emotional | 27.02 Scores on a scale | Standard Error 21.85 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M60 change from baseline - Emotional | 21.4 Scores on a scale | Standard Error 24.53 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M3 change from baseline - Social | 7.6 Scores on a scale | Standard Error 13.9 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M6 change from baseline - Social | 8.4 Scores on a scale | Standard Error 17.04 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M12 change from baseline - Social | 14.8 Scores on a scale | Standard Error 16.68 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M24 change from baseline - Social | 17.3 Scores on a scale | Standard Error 15.85 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M60 change from baseline - Social | 17.9 Scores on a scale | Standard Error 14.77 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M3 change from baseline - School | 8.9 Scores on a scale | Standard Error 14.35 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M6 change from baseline - School | 10.0 Scores on a scale | Standard Error 16.58 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M12 change from baseline - School | 19.0 Scores on a scale | Standard Error 19.97 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M24 change from baseline - School | 13.9 Scores on a scale | Standard Error 23.98 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M60 change from baseline - School | 17.7 Scores on a scale | Standard Error 24.46 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M3 change from baseline - Physical | 17.5 Scores on a scale | Standard Error 18.36 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M6 change from baseline - Physical | 21.6 Scores on a scale | Standard Error 25.81 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M12 change from baseline - Physical | 31.1 Scores on a scale | Standard Error 28.57 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M24 change from baseline - Physical | 37.4 Scores on a scale | Standard Error 25.12 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M60 change from baseline - Physical | 37.1 Scores on a scale | Standard Error 24.9 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M3 change from baseline - Psychosocial health | 10.4 Scores on a scale | Standard Error 12.38 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M6 change from baseline - Psychosocial health | 11.0 Scores on a scale | Standard Error 14.08 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M12 change from baseline - Psychosocial health | 19.8 Scores on a scale | Standard Error 16.8 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M24 change from baseline - Psychosocial health | 20.1 Scores on a scale | Standard Error 16.34 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M60 change from baseline - Psychosocial health | 18.9 Scores on a scale | Standard Error 15.15 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M3 change from baseline - Total score | 13.0 Scores on a scale | Standard Error 13.28 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M6 change from baseline - Total score | 14.8 Scores on a scale | Standard Error 17 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M12 change from baseline - Total score | 2.8 Scores on a scale | Standard Error 19.56 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M24 change from baseline - Total score | 26.2 Scores on a scale | Standard Error 16.7 |
| Main Cohort: Single Dose of CTL019 | Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire | M60 change from baseline - Total score | 25.3 Scores on a scale | Standard Error 15.45 |
Secondary
Event-free Survival Per IRC Assessment
EFS is the time from date of tisagenlecleucel infusion to the earliest of death, relapse or treatment failure.
Time frame: 60 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Event-free Survival Per IRC Assessment | 23.7 months |
| Cohort 1: Single Dose of CTL019 | Event-free Survival Per IRC Assessment | NA months |
Secondary
Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Bone Marrow by Day 28 Response by IRC Assessment
This is the summary cellular kinetic concentrations for CTL019 by flow cytometry. It evaluated the persistence of transduced CTL019 cells post-infusion. Observation was up to Month 6 for bone marrow.
Time frame: Month 6
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel parameter under investigation. Analysis of this particular outcome included a subset of PAS who had evaluation data of the parameter at the specific timepoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Bone Marrow by Day 28 Response by IRC Assessment | 0.519 Percentage of CD3+/CTL019+ cells | Geometric Coefficient of Variation 185.8 |
| Cohort 1: Single Dose of CTL019 | Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Bone Marrow by Day 28 Response by IRC Assessment | 0.1 Percentage of CD3+/CTL019+ cells | — |
Secondary
Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Peripheral Blood by Day 28 Disease Response Per IRC Assessment
This is the summary cellular kinetic concentrations for CTL019 by flow cytometry in peripheral blood. It evaluated the persistence of transduced CTL019 cells post-infusion. Observation was up to Month 60 for peripheral blood.
Time frame: Month 60
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel parameter under investigation. Analysis of this particular outcome included a subset of PAS who had evaluation data of the parameter at the specific timepoint. Therefore, no participants in Cohort 1 had at least one blood sample providing evaluable cellular kinetic data for tisagenlecleucel at tis time point, so no data was collected for Cohort 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Peripheral Blood by Day 28 Disease Response Per IRC Assessment | 0.253 Percentage of CD3+/CTL019+ cells | Geometric Coefficient of Variation 67.4 |
Secondary
Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers)
Profile of soluble immune factors of key inflammatory markers and cytokine parameters in blood by maximum CRS grade that may be key to cytokine release syndrome (CRS).
Time frame: Maximum post-baseline (approx. 60 months)
Population: Safety Set: The Safety set comprised all patients who received tisagenlecleucel infusion with evaluable data. This analysis included a subset of Safety set who had any data of the particular biomarker at the specific timepoint. Therefore, no participants in Cohort 1 had biomarker data at this time point, so no data was collected for Cohort 1.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Interferon gamma: Fold-change from BL Grade 4 CRS | 2745.92 fold-change from baseline | Geometric Coefficient of Variation 1186.3 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Interleukin 10: Fold-change from BL Grade 4 CRS | 179.49 fold-change from baseline | Geometric Coefficient of Variation 966.7 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Interleukin 12p70: Fold-change from BL Grade 4 CRS | 93.50 fold-change from baseline | Geometric Coefficient of Variation 261 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Interleukin 13: Fold-change from BL Grade 4 CRS | 49.21 fold-change from baseline | Geometric Coefficient of Variation 124 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Interleukin 1 beta: Fold-change from BL Grade 4 CRS | 16.75 fold-change from baseline | Geometric Coefficient of Variation 127.7 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Interleukin 2: Fold-change from BL Grade 4 CRS | 337.86 fold-change from baseline | Geometric Coefficient of Variation 161.1 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Interleukin 4: Fold-change from BL Grade 4 CRS | 170.21 fold-change from baseline | Geometric Coefficient of Variation 163.3 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Interleukin 6: Fold-change from BL Grade 4 CRS | 1435.85 fold-change from baseline | Geometric Coefficient of Variation 221.6 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Interleukin 8: Fold-change from BL Grade 4 CRS | 139.40 fold-change from baseline | Geometric Coefficient of Variation 246.9 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers) | Tumor necrosis factor alpha: Fold-change from BL Grade 4 CRS | 27.13 fold-change from baseline | Geometric Coefficient of Variation 223.7 |
Secondary
Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (C Reactive Protein & Ferritin)
Profile of soluble immune factors of key inflammatory markers and cytokine parameters in blood by maximum CRS grade that may be key to cytokine release syndrome (CRS).
Time frame: Maximum post-baseline (approx. 60 months)
Population: Safety Set: The Safety set comprised all patients who received tisagenlecleucel infusion with evaluable data. This analysis included a subset of Safety set who had any data of the particular biomarker at the specific timepoint. Therefore, no participants in Cohort 1 had biomarker data at this time point, so no data was collected for Cohort 1.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (C Reactive Protein & Ferritin) | C Reactive Protein: Fold-change from BL Grade 4 CRS | 9.33 fold-change from baseline | Geometric Coefficient of Variation 303.9 |
| Main Cohort: Single Dose of CTL019 | Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (C Reactive Protein & Ferritin) | Ferritin: Fold-change from BL Grade 4 CRS | 36.62 fold-change from baseline | Geometric Coefficient of Variation 164.6 |
Secondary
Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) After Tisagenlecleucel (CTL019) Infusion
These are the participants who achieved CR or CRi and then proceeded to SCT after being infused by tisagenlecleucel.
Time frame: up to 6 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) After Tisagenlecleucel (CTL019) Infusion | 18 Participants |
| Cohort 1: Single Dose of CTL019 | Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) After Tisagenlecleucel (CTL019) Infusion | 0 Participants |
Secondary
Overall Survival (OS)
OS, is the time from date of tisagenlecleucel infusion to the date of death due to any reason.
Time frame: 60 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Overall Survival (OS) | NA months |
| Cohort 1: Single Dose of CTL019 | Overall Survival (OS) | NA months |
Secondary
Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion
Levels of B and T cells (blood and bone marrow) prior to and following CTL019 infusion for safety monitoring
Time frame: Month 3, Month 12, Maximum post-baseline (approx. 60 months)
Population: Safety Set: The Safety set comprised all patients who received tisagenlecleucel infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | Maximum post-BL: (T cell) All participants | 34.12 percentage change from baseline | Standard Deviation 29.45 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M3: % change from BL - (B cell) CR/CRi | -25.37 percentage change from baseline | Standard Deviation 31.693 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | Maximum post-BL: (B cell) All participants | -15.60 percentage change from baseline | Standard Deviation 40.336 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M3: % change from BL - (T cell) All participants | -11.91 percentage change from baseline | Standard Deviation 32.333 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M12: % change from BL - (T cell) All participants | -1.68 percentage change from baseline | Standard Deviation 36.228 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | Maximum post-BL: (B cell) NR | 2.10 percentage change from baseline | Standard Deviation 66.398 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M3: % change from BL - (B cell) NR | -37.93 percentage change from baseline | Standard Deviation 35.882 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M3: % change from BL - (B cell) Unknown | -11.01 percentage change from baseline | Standard Deviation 6.649 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M3: % change from BL - (B cell) All participants | -24.23 percentage change from baseline | Standard Deviation 30.215 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M12: % change from BL - (B cell) CR/CRi | -18.55 percentage change from baseline | Standard Deviation 27.144 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M12: % change from BL - (B cell) NR | -55.21 percentage change from baseline | — |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M12: % change from BL - (B cell) Unknown | -12.04 percentage change from baseline | Standard Deviation 5.995 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M12 % change from BL -: (B cell) All Participants | -19.00 percentage change from baseline | Standard Deviation 26.432 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | Maximum post-BL: (B cell) CR/CRi | -21.25 percentage change from baseline | Standard Deviation 37.618 |
| Main Cohort: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | Maximum post-BL: (B cell) Unknown | 7.98 percentage change from baseline | Standard Deviation 29.536 |
| Cohort 1: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M3: % change from BL - (B cell) CR/CRi | -0.51 percentage change from baseline | — |
| Cohort 1: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | M3: % change from BL - (B cell) All participants | -0.51 percentage change from baseline | — |
| Cohort 1: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | Maximum post-BL: (B cell) All participants | 6.06 percentage change from baseline | — |
| Cohort 1: Single Dose of CTL019 | Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion | Maximum post-BL: (B cell) CR/CRi | 6.06 percentage change from baseline | — |
Secondary
Percentage of Participants Attaining CR or CRi at Day 28 +/- 4 Days Post Tisagenlecleucel (CTL019) Infusion by IRC Assessment
These are participants who had a day 28 response (CR or CRi response) by IRC assessment.
Time frame: 1 month
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage of Participants Attaining CR or CRi at Day 28 +/- 4 Days Post Tisagenlecleucel (CTL019) Infusion by IRC Assessment | 78.5 Percentage of participants |
| Cohort 1: Single Dose of CTL019 | Percentage of Participants Attaining CR or CRi at Day 28 +/- 4 Days Post Tisagenlecleucel (CTL019) Infusion by IRC Assessment | 100 Percentage of participants |
Secondary
Percentage of Participants Who Achieved CR or CRi and Then Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) While in Remission Prior to Month 6 Resoonse
These are the participants who achieved CR or CRi and then proceeded to HSCT while in remission prior to Month 6 response assessment
Time frame: 6 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage of Participants Who Achieved CR or CRi and Then Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) While in Remission Prior to Month 6 Resoonse | 7.6 Percentage of Participants |
| Cohort 1: Single Dose of CTL019 | Percentage of Participants Who Achieved CR or CRi and Then Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) While in Remission Prior to Month 6 Resoonse | 0.0 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved CR or CRi Without Hematopoietic Stem Cell Transplantation (HSCT)
These are the participants who achieved CR or CRi without HSCT between tisagenlecleucel (CTL019) infusion and Month 6 response assessment.
Time frame: 6 months after tisagenlecleucel administration
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage of Participants Who Achieved CR or CRi Without Hematopoietic Stem Cell Transplantation (HSCT) | 60.8 Percentage of participants |
| Cohort 1: Single Dose of CTL019 | Percentage of Participants Who Achieved CR or CRi Without Hematopoietic Stem Cell Transplantation (HSCT) | 100.0 Percentage of participants |
Secondary
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From Fraunhofer Institute Manufacturing Facility as Per IRC
These are the percentage of participants who achieved Best Overall Response (BOR) of CR or CRi with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from Fraunhofer Institute manufacturing facilities only, by IRC assessment.
Time frame: 3 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel from Fraunhofer Institue Manufacturing Facility. Participants in Cohort 1 were from the Fraunhofer Institute manufacturing facility and not the US where the data was collected from, so no data was collected for this Cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From Fraunhofer Institute Manufacturing Facility as Per IRC | 75.0 Percentage of participants |
Secondary
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From US Manufacturing Facility as Per IRC in the Main Cohort Only (Key Secondary)
These are the percentage of participants who achieved Best Overall Response (BOR) of complete response (CR) or complete response with incomplete blood count recovery (CRi) with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from US manufacturing facilities only, by IRC assessment.
Time frame: 3 months after tisagenlecleucel administration
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel from US manufacturing facilities.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From US Manufacturing Facility as Per IRC in the Main Cohort Only (Key Secondary) | 82.1 Percentage of participants |
p-value: <0.0001Clopper-Pearson
Secondary
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With MRD Negative Bone Marrow by Flow Cytometry From All Manufacturing Facilities as Per IRC in the Main Cohort Only (Key Secondary)
These are the percentage of participants who achieved Best Overall Response (BOR) of CR or CRi with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from all manufacturing facilities by IRC assessment. MRD negative = MRD% \< 0.01%
Time frame: 3 months after tisagenlecleucel administration
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel from all manufacturing facilities.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage of Participants With Best Overall Response (BOR) of CR or CRi With MRD Negative Bone Marrow by Flow Cytometry From All Manufacturing Facilities as Per IRC in the Main Cohort Only (Key Secondary) | 81.0 Percentage of participants |
p-value: <0.0001Clopper-Pearson
Secondary
Percentage of Participants With Overall Remission Rate (ORR) as Per IRC From US Manufacturing Facilities in the Main Cohort Only (Key Secondary)
These are the percentage of participants with ORR who achieved overall remission rate which includes complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by IRC assessment after having been infused with tisagenlecleucel from US manufacturing facilities.
Time frame: 3 months after tisagenlecleucel administration
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel from US manufacturing facilities.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage of Participants With Overall Remission Rate (ORR) as Per IRC From US Manufacturing Facilities in the Main Cohort Only (Key Secondary) | 82.1 Percentage of participants |
Secondary
Percentage of Participants With Overall Remission Rate (ORR) - From Fraunhofer Institute Manufacturing Facility
These are the percentage of participants with ORR who achieved overall remission rate which includes complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by IRC assessment after having been infused with tisagenlecleucel from Fraunhofer Institute manufacturing facility.
Time frame: 60 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel from Fraunhofer Institue Manufacturing Facility. Participants in Cohort 1 were from the Fraunhofer Institute manufacturing facility and not the US where the data was collected from, so no data was collected for this Cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Percentage of Participants With Overall Remission Rate (ORR) - From Fraunhofer Institute Manufacturing Facility | 83.3 Percentage of participants |
Secondary
Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC
Persistence is defined as the time corresponding to last quantifiable transgene level in peripheral blood (Tlast), reported by CR/CRi, no response (NR), Unknown and by All participants. D28 refers to the timepoint for definition of responder populations, whereas M60 is the actual timepoint for endpoint assessment.
Time frame: 60 months
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC | Tlast CR/CRi | 232 days |
| Main Cohort: Single Dose of CTL019 | Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC | Tlast NR | 48.5 days |
| Main Cohort: Single Dose of CTL019 | Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC | Tlast Unknown | 220 days |
| Main Cohort: Single Dose of CTL019 | Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC | Tlast All Participants | 179 days |
| Cohort 1: Single Dose of CTL019 | Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC | Tlast CR/CRi | 89.7 days |
| Cohort 1: Single Dose of CTL019 | Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC | Tlast All Participants | 89.7 days |
Secondary
Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC
AUC (area under curve) from day of infusion to day 28 or other disease assessment days, in peripheral blood (% or copies/μg x days), reported by CR/CRi, no response (NR), Unknown and by All participants. D28 refers to the timepoint for definition of responder populations, whereas 84 days is the actual timepoint for endpoint assessment. : AUC is defined based on the time window i.e., AUC from 0 to 84 days after infusion. Therefore, the time frame specifies the maximum time for up to which the data are used for estimation of AUC (84 days for AUC84d).
Time frame: 0 to 84 days after infusion
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC0-28d: CR/CRi | 310000 copies/ug*days | Geometric Coefficient of Variation 192.2 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC 0-84d: CR/CRi | 462000 copies/ug*days | Geometric Coefficient of Variation 230.1 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC 0-84d: NR | 1130000 copies/ug*days | Geometric Coefficient of Variation 75.5 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC 0-84d: Unknown | 984000 copies/ug*days | Geometric Coefficient of Variation 202.4 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC 0-84d: All Participants | 521000 copies/ug*days | Geometric Coefficient of Variation 225.3 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC0-28d: NR | 301000 copies/ug*days | Geometric Coefficient of Variation 116.9 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC0-28d: Unknown | 768000 copies/ug*days | Geometric Coefficient of Variation 177.4 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC0-28d: All Participants | 341000 copies/ug*days | Geometric Coefficient of Variation 190.9 |
| Cohort 1: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC0-28d: CR/CRi | 31500 copies/ug*days | — |
| Cohort 1: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC0-28d: All Participants | 31500 copies/ug*days | — |
| Cohort 1: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC 0-84d: All Participants | 74700 copies/ug*days | — |
| Cohort 1: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | AUC 0-84d: CR/CRi | 74700 copies/ug*days | — |
Secondary
Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC
Cmax is the maximum (peak) observed in peripheral blood drug concentration after single dose administration reported by CR/CRi, no response (NR), Unknown and by All participants. D28 refers to the timepoint for definition of responder populations, whereas M60 is the actual timepoint for endpoint assessment. The reported Cmax is the summary of maximum level observed based on the data from each patient and based on all the data that's been collected for up to 60 months in a patient.
Time frame: 60 months
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | CR/CRi | 37200 copies/ug | Geometric Coefficient of Variation 154.2 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | NR | 31700 copies/ug | Geometric Coefficient of Variation 87.4 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | Unknown | 67700 copies/ug | Geometric Coefficient of Variation 132.5 |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | All Participants | 39200 copies/ug | Geometric Coefficient of Variation 148.8 |
| Cohort 1: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | CR/CRi | 2690 copies/ug | — |
| Cohort 1: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | All Participants | 2690 copies/ug | — |
Secondary
Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC
Tmax is the time to reach maximum (peak) peripheral blood drug concentration after single dose administration (days), reported by CR/CRi, no response (NR), Unknown and by All participants. D28 refers to the timepoint for definition of responder populations, whereas M60 is the actual timepoint for endpoint assessment. The time frame of 60 months refers to the duration for which the data were reviewed to identify the time of Cmax for this measure.
Time frame: 60 months
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | CR/CRi | 9.87 days |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | NR | 20.9 days |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | Unknown | 13.4 days |
| Main Cohort: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | All Participants | 9.98 days |
| Cohort 1: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | CR/CRi | 8.55 days |
| Cohort 1: Single Dose of CTL019 | Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC | All Participants | 8.55 days |
Secondary
Prevalence and Incidence of Immunogenicity to Tisagenlecleucel (CTL019)
This is defined as the percentage of participants who tested positive for anti-mCAR19 antibodies at any time post-baseline, reported by CR/CRi, no response (NR), Unknown and by All participants. .
Time frame: At any time post-baseline, up to a max. of 60 months
Population: Safety Set: The Safety set comprised all patients who received tisagenlecleucel infusion in the Main Cohort. No participants in Cohort 1 had immunogenicity data providing evaluable cellular kinetic data for tisagenlecleucel at this time point, so no data was collected for Cohort 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Prevalence and Incidence of Immunogenicity to Tisagenlecleucel (CTL019) | CR/CRi positive | 61 Participants |
| Main Cohort: Single Dose of CTL019 | Prevalence and Incidence of Immunogenicity to Tisagenlecleucel (CTL019) | NR positive | 6 Participants |
| Main Cohort: Single Dose of CTL019 | Prevalence and Incidence of Immunogenicity to Tisagenlecleucel (CTL019) | Unknown positive | 11 Participants |
| Main Cohort: Single Dose of CTL019 | Prevalence and Incidence of Immunogenicity to Tisagenlecleucel (CTL019) | All Patients positive | 78 Participants |
Secondary
Relapse-free Survival Per IRC Assessment
RFS is the time from achievement of CR or CRi at any time post-infusion, whichever occurs first, to relapse or death due to any cause during CR or CRi.
Time frame: 60 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Cohort: Single Dose of CTL019 | Relapse-free Survival Per IRC Assessment | 46.8 months |
| Cohort 1: Single Dose of CTL019 | Relapse-free Survival Per IRC Assessment | NA months |
Secondary
Response as a Function of Baseline Tumor Burden (Tumor Load) in Main Cohort Only
Percentage of participants who achieved BOR of CR or CRi by flow cytometry as a function of baseline bone marrow tumor burden.
Time frame: 3 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel with a baseline tumor burden assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Response as a Function of Baseline Tumor Burden (Tumor Load) in Main Cohort Only | Baseline bone marrow tumor burden: Low (<50%) | 96.0 Percentage of participants |
| Main Cohort: Single Dose of CTL019 | Response as a Function of Baseline Tumor Burden (Tumor Load) in Main Cohort Only | Baseline bone marrow tumor burden: High (>=50%) | 75.9 Percentage of participants |
| Cohort 1: Single Dose of CTL019 | Response as a Function of Baseline Tumor Burden (Tumor Load) in Main Cohort Only | Baseline bone marrow tumor burden: Low (<50%) | 100.0 Percentage of participants |
Secondary
Site of Involvement of Subsequent Relapse
Anatomical location of relapse in participants who achieved prior CR/CRi subsequent to tisagenlecleucel infusion.
Time frame: 60 months
Population: FAS: The Full analysis set comprised all patients who received infusion of tisagenlecleucel and who achieved CR or CRi. Achieving CR or CRi requireb confirmation but for this analysis, all patients with one CR/CRi, regardless of confirmation were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Site of Involvement of Subsequent Relapse | BM and/or blood relapse | 23 Participants |
| Main Cohort: Single Dose of CTL019 | Site of Involvement of Subsequent Relapse | Extramedullary only | 2 Participants |
| Main Cohort: Single Dose of CTL019 | Site of Involvement of Subsequent Relapse | Unknown | 4 Participants |
Secondary
Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow by Day 28 Response by IRC Assessment
This is the summary of cellular kinetic concentrations for Tisagenlecleucel (CTL019) transgene levels by qPCR in bone marrow.
Time frame: Month 6
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel parameter under investigation. Analysis of this particular outcome included a subset of PAS who had evaluation data of the parameter at the specific timepoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow by Day 28 Response by IRC Assessment | 210 copies/ug DNA | Geometric Coefficient of Variation 138.1 |
| Cohort 1: Single Dose of CTL019 | Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow by Day 28 Response by IRC Assessment | NA copies/ug DNA | — |
Secondary
Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow - Tisagenlecleucel Manufactured From Fraunhofer Institute
This is the summary of cellular kinetic concentrations for Tisagenlecleucel (CTL019) transgene levels by qPCR, by disease response in bone marrow by IRC assessment. The assessment of the efficacy, safety and in vivo cellular pharmacokinetics are for patients infused with tisagenlecleucel manufactured by Fraunhofer Institute.
Time frame: Month 3
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel. Participants in Cohort 1 were from the Fraunhofer Institute manufacturing facility and not the US where the data was collected from, so no data was collected for this Cohort.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow - Tisagenlecleucel Manufactured From Fraunhofer Institute | 855 copies/ug | Geometric Coefficient of Variation 792.6 |
Secondary
Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood by Day 28 Response by Independent Review Committee (IRC) Assessment
This is the summary of cellular kinetic concentrations for Tisagenlecleucel (CTL019) transgene levels by qPCR in peripheral blood.
Time frame: Month 60
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel. Analysis of this particular outcome included a subset of PAS who had evaluation data of the parameter at the specific timepoint. Therefore, no participants in Cohort 1 had at least one blood sample providing evaluable cellular kinetic data for tisagenlecleucel at tis time point, so no data was collected for Cohort 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood by Day 28 Response by Independent Review Committee (IRC) Assessment | 207 copies/ug DNA | Geometric Coefficient of Variation 95.5 |
Secondary
Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood - Tisagenlecleucel Manufactured From Fraunhofer Institute
This is the summary of cellular kinetic concentrations for Tisagenlecleucel (CTL019) transgene levels by qPCR, by disease response in blood by IRC assessment. The assessment of the efficacy, safety and in vivo cellular pharmacokinetics are for patients infused with tisagenlecleucel manufactured by Fraunhofer Institute.
Time frame: Month 60
Population: PAS: The PAS consisted of patients in the FAS who had at least one sample providing evaluable cellular kinetic data for tisagenlecleucel from Fraunhofer Institue Manufacturing Facility. Participants in Cohort 1 were from the Fraunhofer Institute manufacturing facility and not the US where the data was collected from, so no data was collected for this Cohort.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood - Tisagenlecleucel Manufactured From Fraunhofer Institute | 42800 copies/ug | Geometric Coefficient of Variation 117.7 |
Post Hoc
All Collected Deaths
On-treatment deaths, which include post-treatment survival follow-up deaths, were collected during the post-infusion period (starting at the day of first infusion) until the end of the study, approx. 60 months. All deaths refers to the sum of on-treatment deaths and post-treatment survival follow-up deaths up to approx. 60 months.
Time frame: On-treatment deaths: Up to 60 months; Post-treatment survival follow-up deaths: Up to approx. 60 months
Population: Clinical Database Population: all infused participants in the Main cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Cohort: Single Dose of CTL019 | All Collected Deaths | On-treatment deaths include post-treatment survival follow-up deaths | 33 Participants |
| Main Cohort: Single Dose of CTL019 | All Collected Deaths | All deaths | 33 Participants |
| Cohort 1: Single Dose of CTL019 | All Collected Deaths | On-treatment deaths include post-treatment survival follow-up deaths | 0 Participants |
| Cohort 1: Single Dose of CTL019 | All Collected Deaths | All deaths | 0 Participants |