Acute Lymphoblastic Leukemia
Conditions
Keywords
acute lymphoblastic leukemia, ALL, chimeric antigen receptor, CAR, CAR T cells, JCAR015, autologous T cell therapy, cell therapy
Brief summary
This single-arm, multicenter Phase 2 trial will treat adult patients who have relapsed or refractory B-ALL with an infusion of the patient's own T cells that have been genetically modified to express a chimeric antigen receptor (CAR) that will bind to leukemia cells that express the CD19 protein on the cell surface. The study will determine if these modified T cells (called JCAR015) help the body's immune system eliminate leukemia cells. The trial will also study the safety of treatment with JCAR015, how long JCAR015 cells stay in the patient's body, the extent to which JCAR015 eliminates minimal residual disease, and the impact of this treatment on survival.
Detailed description
This is a single-arm, multicenter Phase 2 study to determine the efficacy and safety of JCAR015 in adult patients with relapsed or refractory B-ALL. The study will have the following sequential phases: Part A (screening, leukapheresis, cell product preparation, and cytoreductive chemotherapy) and Part B (treatment and follow-up). The follow-up period for each participant is approximately 12 months after the final JCAR015 infusion. The total duration of the study is expected to be approximately 3 years. Long-term follow-up for survival, toxicity, and viral vector safety will continue under a separate long-term follow-up protocol per health regulatory authority guidelines, currently up to 15 years after the last JCAR015 infusion.
Interventions
BIOLOGICALJCAR015 (CD19-targeted CAR T cells)
Part A: Following leukapheresis and concurrent with generation of JCAR015, participants received, at the Investigator's discretion, cytoreductive chemotherapy based on the Investigator's choice of regimens and/or supportive care. Part B: Participants who were eligible for treatment in Part B received two IV doses of JCAR015 CAR T cells separated by 14 to 28 days. JCAR015 infusion was preceded by lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine.
Sponsors
Juno Therapeutics, a Subsidiary of Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years at the time of consent 2. Relapsed or refractory B-ALL, defined as: * First or greater bone marrow relapse from CR, or * Any bone marrow relapse after allogeneic hematopoietic stem cell transplant (HSCT); subjects must be at least 100 days from HSCT at the time of screening and off immunosuppressant medication for at least 1 month at the time of screening, and have no active graft-vs-host disease (GVHD), or * Refractory B-ALL, defined by not having achieved a CR or CRi after two attempts at remission induction using standard regimens, or * Ph+ B-ALL if subjects are intolerant to or ineligible for tyrosine kinase inhibitor (TKI) therapy, or have progressed after at least one line of TKI therapy 3. Morphological evidence of disease in bone marrow (at least 5% blasts) 4. Evidence of CD19 expression 5. Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2 at the time of screening 6. Adequate pulmonary, renal, hepatic, and cardiac function 7. Adequate central or peripheral vascular access for leukapheresis procedure
Exclusion criteria
1. Isolated extramedullary disease relapse 2. Concomitant genetic syndrome or other known bone marrow failure syndrome 3. Burkitt's lymphoma/leukemia or chronic myelogenous leukemia lymphoid blast crisis (p210 BCR-ABL+) 4. Prior malignancy, unless treated with curative intent and with no evidence of active disease present for \> 5 years before screening 5. Prior treatment with any gene therapy product 6. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening 7. Systemic fungal, bacterial, viral, or other infection that is not controlled, at the time of screening 8. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening 9. Active central nervous system (CNS) involvement by malignancy (defined as CNS-3 per National Comprehensive Cancer Network \[NCCN\] guidelines) 10. History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease 11. History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis 12. Participation in an investigational research study using an investigational agent within 30 days of screening 13. History of treatment with a murine-derived biological product other than blinatumomab unless subject has been shown to be negative for human-anti-mouse-antibodies (HAMA) prior to or during screening 14. Pregnant or nursing women 15. Use of prohibited medications: 1. Steroids: Therapeutic doses of corticosteroids are prohibited within 7 days prior to leukapheresis. 2. Allogeneic cellular therapy: Donor lymphocyte infusions (DLI) are prohibited within 4 weeks prior to leukapheresis 3. GVHD therapies: Any drug used for GVHD within 4 weeks prior to leukapheresis 4. Chemotherapies: Salvage chemotherapy must be stopped at least 1 week prior to leukapheresis 16. Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematopoietic Recovery (CRi), as Determined by an Independent Review Committee (IRC) | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | Overall remission rate (ORR) is defined as the percentage of participants with CR or CRi based on IRC assessment. For CR, all of the following must be met: (1) in bone marrow, trilineage hematopoiesis and \< 5% blasts; (2) in peripheral blood, neutrophils \> 1,000/µL, platelets \> 100,000/µL, and circulating blasts \< 1%; (3) no clinical evidence of extramedullary disease by physical examination and no symptoms suggestive of CNS involvement (if additional assessments such as CSF assessment by lumbar puncture or Ommaya reservoir tap, CNS imaging, or biopsy are performed, results must show no evidence of disease); (4) no platelet and/or neutrophil transfusions ≤ 7 days before the date of peripheral blood sampling, and (5) no clinical evidence of recurrence for 4 weeks. For CRi, all criteria for CR are met except that one or more of the following exists in the peripheral blood: neutrophils ≤ 1,000/µL, platelets ≤ 100,000/µL, or platelet transfusions ≤ 7 days before blood sampling. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | Best overall response (BOR) is defined as the best disease response recorded from the time of the last JCAR015 infusion until the start of another anticancer therapy (refer to Outcome Measure #1 for criteria for CR and CRi). |
| Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | Percentage of participants who achieved a CR or CRi, as determined by an IRC, with no evidence of MRD in the bone marrow (refer to Outcome Measure #1 for criteria for CR and CRi). MRD-negative is defined as undetectable leukemic cells in the bone marrow as determined by a polymerase chain reaction (PCR)-based assay. |
| Percentage of Participants Who Achieved a MRD-Negative CR or CRi | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | Percentage of participants who achieved a CR or CRi, as determined by an IRC, with no evidence of MRD in the bone marrow (refer to Outcome Measure #1 for criteria for CR and CRi). MRD-negative is defined as undetectable leukemic cells in the bone marrow as determined by a PCR-based assay. |
| Relapse-Free Survival (RFS), as Determined by an IRC | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | RFS is defined as the interval from the first documentation of CR or CRi (refer to Outcome Measure #1) to the earlier date of relapse or death due to any cause. Participants who proceeded to hematopoietic stem cell transplant (HSCT) after JCAR015 infusion were censored at the time of HSCT. |
| RFS, as Determined by an IRC | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | RFS is defined as the interval from the first documentation of CR or CRi (refer to Outcome Measure #1) to the earlier date of relapse or death due to any cause. Participants who proceeded to HSCT after JCAR015 infusion were censored at the time of HSCT. |
| Event-Free Survival (EFS) | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | EFS is defined as the time from the date of the first JCAR015 infusion to the earliest of the following events: death from any cause, relapse, or treatment failure (defined as no response and subsequent discontinuation from the study for adverse event, lack of efficacy or progressive disease, or new anticancer therapy). Participants who proceeded to HSCT after JCAR015 infusion were censored at the time of HSCT. |
| EFS | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | EFS is defined as the time from the date of the first JCAR015 infusion to the earliest of the following events: death from any cause, relapse, or treatment failure (defined as no response and subsequent discontinuation from the study for adverse event, lack of efficacy or progressive disease, or new anticancer therapy). Participants who proceeded to HSCT after JCAR015 infusion were censored at the time of HSCT. |
| Overall Survival (OS) | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | OS is defined as the interval from the date of the first JCAR015 infusion to the date of death due to any reason. |
| OS | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | OS is defined as the interval from the date of the first JCAR015 infusion to the date of death due to any reason. |
| Percentage of Participants With CR or CRi, as Determined by an IRC | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | ORR is defined as the percentage of participants with CR or CRi based on IRC assessment (refer to criteria in Outcome Measure #1) |
| Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC, at Month 6 After the Final JCAR015 Infusion | Day 1 (first JCAR015 infusion) up to 6 months after the last JCAR015 infusion | ORR at Month 6 is defined as the percentage of participants who achieved a CR or CRi at Month 6 after the final JCAR015 infusion without HSCT during the time period between the final JCAR015 infusion and the Month 6 response assessment (refer to Outcome Measure #1 for criteria for CR and CRi). |
| Percentage of Participants Who Achieved a Morphologic Remission Within 6 Months After the Final JCAR015 Infusion and Then Proceeded to HSCT | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | Percentage of participants who achieved a morphologic remission within 6 months after the final JCAR015 infusion and then proceeded to HSCT prior to 12 months after the final JCAR015 infusion |
| Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Quantitative Polymerase Chain Reaction (qPCR) | Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable) | Cmax is defined as the highest measured number of copies of JCAR015 transgene per microgram of genomic DNA in peripheral blood cells as assessed by qPCR. |
| Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Flow Cytometry | Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable) | Cmax is defined as the highest measured concentration of JCAR015 CAR T cells per microliter of peripheral blood as measured by flow cytometry. |
| Time to Maximum Concentration of JCAR015 (Tmax) in the Peripheral Blood as Measured by qPCR | Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable) | Tmax is defined as the time after the JCAR015 infusion at which the maximum concentration (Cmax) as measured by qPCR is observed. If Cmax occurred after the second infusion, Tmax was calculated from the time of the second infusion. |
| Tmax in the Peripheral Blood as Measured by Flow Cytometry | Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable) | Tmax is defined as the time after the JCAR015 infusion at which the Cmax as measured by flow cytometry of the JCAR015 CAR is observed. If Cmax occurred after the second infusion, Tmax was calculated from the time of the second infusion. |
| Area Under the Concentration-vs-Time Curve (AUC) for JCAR015 in the Peripheral Blood as Measured by qPCR | Pre-dose Day 1 of the first JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion | AUC is defined as the area under the concentration-vs-time curve from Day 1 to Day 29 after the first JCAR015 infusion as measured by qPCR of the JCAR015 transgene. AUC calculation includes pharmacokinetic (PK) results up to the second JCAR015 infusion for subjects who received the second infusion prior to Day 29 after the first JCAR015 infusion. |
| AUC for JCAR015 in the Peripheral Blood as Measured by Flow Cytometry | Pre-dose Day 1 of the first JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion | AUC is defined as the area under the concentration-vs-time curve from Day 1 to Day 29 after the first JCAR015 infusion as measured by flow cytometry of the JCAR015 CAR. AUC calculation includes PK results up to the second JCAR015 infusion for subjects who received the second infusion prior to Day 29 after the first JCAR015 infusion. |
| Percentage of Participants Who Developed Anti-Therapeutic Antibodies Against JCAR015 | Part B Screening; Day 14 after the first JCAR015 infusion; Pre-Dose Day 1 of the second JCAR015 infusion; Day 14 after the second JCAR015 infusion; and Day 28, Month 3, Month 6, and Month 12 after the last JCAR015 infusion | Percentage of participants who developed anti-therapeutic antibodies against JCAR015 |
| Duration of Remission (DOR) as Determined by an IRC | Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion | DOR is defined as the interval from the first documentation of CR or CRi to the earlier date of relapse or death due to ALL. |
Countries
United States
Participant flow
Recruitment details
A total of 82 participants were enrolled at 15 study centers within the United States.
Pre-assignment details
Participants were adults with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (ALL).
Participants by arm
| Arm | Count |
|---|---|
| JCAR015 Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 12-Month Follow-up Period | Death | 5 |
| 12-Month Follow-up Period | Disease progression | 22 |
| 12-Month Follow-up Period | Subject received alternative therapy | 2 |
| 12-Month Follow-up Period | Subject transferred to hospice | 1 |
| 12-Month Follow-up Period | Underwent stem cell transplant | 5 |
| Part A Screening Through Leukapheresis | Disease progression | 1 |
| Part A Screening Through Leukapheresis | Failure to meet criteria for Part A | 22 |
| Part A Screening Through Leukapheresis | Study placed on clinical hold by FDA | 2 |
| Part B Screening | Adverse Event | 1 |
| Part B Screening | Change in diagnosis, no longer eligible | 2 |
| Part B Screening | Death | 2 |
| Part B Screening | Physician Decision | 1 |
| Part B Screening | Study placed on clinical hold by FDA | 7 |
| Part B Screening | Unable to manufacture JCAR015 | 3 |
| Part B Screening | Withdrawal by Subject | 1 |
| Study Treatment | Death | 1 |
| Study Treatment | Study placed on clinical hold by FDA | 1 |
Baseline characteristics
| Characteristic | JCAR015 |
|---|---|
| Age, Continuous | 39 years |
| Age, Customized 39 or younger | 19 Participants |
| Age, Customized 40 to 64 | 15 Participants |
| Age, Customized 65 or older | 4 Participants |
| Eastern Cooperative Oncology Group (ECOG) Score 0 | 3 Participants |
| Eastern Cooperative Oncology Group (ECOG) Score 1 | 29 Participants |
| Eastern Cooperative Oncology Group (ECOG) Score 2 | 5 Participants |
| Eastern Cooperative Oncology Group (ECOG) Score 3 | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Most Recent Prior Regimen Blinatumomab monotherapy | 11 Participants |
| Most Recent Prior Regimen Investigational agent | 1 Participants |
| Most Recent Prior Regimen Marqibo | 2 Participants |
| Most Recent Prior Regimen Multi-agent chemotherapy | 15 Participants |
| Most Recent Prior Regimen Other | 6 Participants |
| Most Recent Prior Regimen Tyrosine kinase inhibitor alone | 1 Participants |
| Most Recent Prior Regimen Tyrosine kinase inhibitor + chemotherapy | 2 Participants |
| Number of Prior Lines of Therapy | 2 lines of therapy |
| Philadelphia Chromosome Status Philadelphia chromosome negative | 34 Participants |
| Philadelphia Chromosome Status Philadelphia chromosome positive | 4 Participants |
| Prior Stem Cell Transplant Did not receive prior stem cell transplant | 24 Participants |
| Prior Stem Cell Transplant Received prior stem cell transplant | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Response to Most Recent Prior Regimen Missing | 1 Participants |
| Response to Most Recent Prior Regimen No response | 27 Participants |
| Response to Most Recent Prior Regimen Not applicable | 2 Participants |
| Response to Most Recent Prior Regimen Remission | 8 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 28 Participants |
| Time Since Diagnosis | 1.8 years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 38 |
| other Total, other adverse events | 38 / 38 |
| serious Total, serious adverse events | 23 / 38 |
Outcome results
Primary
Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematopoietic Recovery (CRi), as Determined by an Independent Review Committee (IRC)
Overall remission rate (ORR) is defined as the percentage of participants with CR or CRi based on IRC assessment. For CR, all of the following must be met: (1) in bone marrow, trilineage hematopoiesis and \< 5% blasts; (2) in peripheral blood, neutrophils \> 1,000/µL, platelets \> 100,000/µL, and circulating blasts \< 1%; (3) no clinical evidence of extramedullary disease by physical examination and no symptoms suggestive of CNS involvement (if additional assessments such as CSF assessment by lumbar puncture or Ommaya reservoir tap, CNS imaging, or biopsy are performed, results must show no evidence of disease); (4) no platelet and/or neutrophil transfusions ≤ 7 days before the date of peripheral blood sampling, and (5) no clinical evidence of recurrence for 4 weeks. For CRi, all criteria for CR are met except that one or more of the following exists in the peripheral blood: neutrophils ≤ 1,000/µL, platelets ≤ 100,000/µL, or platelet transfusions ≤ 7 days before blood sampling.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes participants with morphological disease at the time of the first JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone and at least one JCAR015 infusion, and who were evaluable for response (excludes 2 subjects with Grade 5 brain edema who died within 8 days after JCAR015 infusion).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JCAR015 | Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematopoietic Recovery (CRi), as Determined by an Independent Review Committee (IRC) | 45.5 percentage of participants |
Secondary
Area Under the Concentration-vs-Time Curve (AUC) for JCAR015 in the Peripheral Blood as Measured by qPCR
AUC is defined as the area under the concentration-vs-time curve from Day 1 to Day 29 after the first JCAR015 infusion as measured by qPCR of the JCAR015 transgene. AUC calculation includes pharmacokinetic (PK) results up to the second JCAR015 infusion for subjects who received the second infusion prior to Day 29 after the first JCAR015 infusion.
Time frame: Pre-dose Day 1 of the first JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion
Population: The analysis population includes all participants who received at least one infusion of JCAR015.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | Area Under the Concentration-vs-Time Curve (AUC) for JCAR015 in the Peripheral Blood as Measured by qPCR | 556520 vector copy number*days/microgram |
Secondary
AUC for JCAR015 in the Peripheral Blood as Measured by Flow Cytometry
AUC is defined as the area under the concentration-vs-time curve from Day 1 to Day 29 after the first JCAR015 infusion as measured by flow cytometry of the JCAR015 CAR. AUC calculation includes PK results up to the second JCAR015 infusion for subjects who received the second infusion prior to Day 29 after the first JCAR015 infusion.
Time frame: Pre-dose Day 1 of the first JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion
Population: The analysis population includes all participants who received at least one infusion of JCAR015.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | AUC for JCAR015 in the Peripheral Blood as Measured by Flow Cytometry | 60.6 cells*days/microliter |
Secondary
Duration of Remission (DOR) as Determined by an IRC
DOR is defined as the interval from the first documentation of CR or CRi to the earlier date of relapse or death due to ALL.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes participants with morphologic disease at the time of JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015, and who achieved a CR or CRi after JCAR015 infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | Duration of Remission (DOR) as Determined by an IRC | 4.4 months |
Secondary
EFS
EFS is defined as the time from the date of the first JCAR015 infusion to the earliest of the following events: death from any cause, relapse, or treatment failure (defined as no response and subsequent discontinuation from the study for adverse event, lack of efficacy or progressive disease, or new anticancer therapy). Participants who proceeded to HSCT after JCAR015 infusion were censored at the time of HSCT.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes all participants who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | EFS | 2.7 months |
Secondary
Event-Free Survival (EFS)
EFS is defined as the time from the date of the first JCAR015 infusion to the earliest of the following events: death from any cause, relapse, or treatment failure (defined as no response and subsequent discontinuation from the study for adverse event, lack of efficacy or progressive disease, or new anticancer therapy). Participants who proceeded to HSCT after JCAR015 infusion were censored at the time of HSCT.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes all participants with morphological disease at the time of the first JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone and at least one infusion of JCAR015.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | Event-Free Survival (EFS) | 0.03 months |
Secondary
Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Flow Cytometry
Cmax is defined as the highest measured concentration of JCAR015 CAR T cells per microliter of peripheral blood as measured by flow cytometry.
Time frame: Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable)
Population: The analysis population includes all participants who received at least one infusion of JCAR015.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Flow Cytometry | 8.1 cells/microliter |
Secondary
Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Quantitative Polymerase Chain Reaction (qPCR)
Cmax is defined as the highest measured number of copies of JCAR015 transgene per microgram of genomic DNA in peripheral blood cells as assessed by qPCR.
Time frame: Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable)
Population: The analysis population includes all participants who received at least one infusion of JCAR015.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Quantitative Polymerase Chain Reaction (qPCR) | 69246 vector copy number/microgram |
Secondary
OS
OS is defined as the interval from the date of the first JCAR015 infusion to the date of death due to any reason.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes all participants who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | OS | 8.15 months |
Secondary
Overall Survival (OS)
OS is defined as the interval from the date of the first JCAR015 infusion to the date of death due to any reason.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes all participants with morphological disease at the time of the first JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone and at least one infusion of JCAR015.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | Overall Survival (OS) | 7.33 months |
Secondary
Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC
Best overall response (BOR) is defined as the best disease response recorded from the time of the last JCAR015 infusion until the start of another anticancer therapy (refer to Outcome Measure #1 for criteria for CR and CRi).
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes all participants with morphological disease at the time of the first JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone and at least one infusion of JCAR015.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| JCAR015 | Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC | CR | 8.3 percentage of participants |
| JCAR015 | Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC | CRi | 33.3 percentage of participants |
Secondary
Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC
BOR is defined as the best disease response recorded from the time of the last JCAR015 infusion until the start of another anticancer therapy (refer to Outcome Measure #1 for criteria for CR and CRi).
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes all participants with morphologic disease at the time of JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| JCAR015 | Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC | CR | 12.5 percentage of participants |
| JCAR015 | Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC | CRi | 34.3 percentage of participants |
Secondary
Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC, at Month 6 After the Final JCAR015 Infusion
ORR at Month 6 is defined as the percentage of participants who achieved a CR or CRi at Month 6 after the final JCAR015 infusion without HSCT during the time period between the final JCAR015 infusion and the Month 6 response assessment (refer to Outcome Measure #1 for criteria for CR and CRi).
Time frame: Day 1 (first JCAR015 infusion) up to 6 months after the last JCAR015 infusion
Population: The analysis population includes all participants who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| JCAR015 | Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC, at Month 6 After the Final JCAR015 Infusion | Maintained CR at Month 6 | 11.1 percentage of participants |
| JCAR015 | Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC, at Month 6 After the Final JCAR015 Infusion | Maintained CRi at Month 6 | 3.7 percentage of participants |
Secondary
Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi
Percentage of participants who achieved a CR or CRi, as determined by an IRC, with no evidence of MRD in the bone marrow (refer to Outcome Measure #1 for criteria for CR and CRi). MRD-negative is defined as undetectable leukemic cells in the bone marrow as determined by a polymerase chain reaction (PCR)-based assay.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes all participants with morphological disease at the time of the first JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone and at least one infusion of JCAR015.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| JCAR015 | Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi | MRD-negative CR/CRi | 41.7 percentage of participants |
| JCAR015 | Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi | MRD-positive CR/CRi | 0 percentage of participants |
| JCAR015 | Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi | MRD-negative CR/CRi unconfirmed | 12.6 percentage of participants |
| JCAR015 | Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi | MRD-positive CR/CRi unconfirmed | 4.2 percentage of participants |
Secondary
Percentage of Participants Who Achieved a Morphologic Remission Within 6 Months After the Final JCAR015 Infusion and Then Proceeded to HSCT
Percentage of participants who achieved a morphologic remission within 6 months after the final JCAR015 infusion and then proceeded to HSCT prior to 12 months after the final JCAR015 infusion
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes participants with morphologic disease at the time of JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015, and who were evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JCAR015 | Percentage of Participants Who Achieved a Morphologic Remission Within 6 Months After the Final JCAR015 Infusion and Then Proceeded to HSCT | 11.1 percentage of participants |
Secondary
Percentage of Participants Who Achieved a MRD-Negative CR or CRi
Percentage of participants who achieved a CR or CRi, as determined by an IRC, with no evidence of MRD in the bone marrow (refer to Outcome Measure #1 for criteria for CR and CRi). MRD-negative is defined as undetectable leukemic cells in the bone marrow as determined by a PCR-based assay.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes all participants with morphologic disease at the time of JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| JCAR015 | Percentage of Participants Who Achieved a MRD-Negative CR or CRi | MRD-negative CR/CRi | 46.9 percentage of participants |
| JCAR015 | Percentage of Participants Who Achieved a MRD-Negative CR or CRi | MRD-positive CR/CRi | 0 percentage of participants |
| JCAR015 | Percentage of Participants Who Achieved a MRD-Negative CR or CRi | MRD-negative CR/CRi unconfirmed | 9.4 percentage of participants |
| JCAR015 | Percentage of Participants Who Achieved a MRD-Negative CR or CRi | MRD-positive CR/CRi unconfirmed | 3.1 percentage of participants |
Secondary
Percentage of Participants Who Developed Anti-Therapeutic Antibodies Against JCAR015
Percentage of participants who developed anti-therapeutic antibodies against JCAR015
Time frame: Part B Screening; Day 14 after the first JCAR015 infusion; Pre-Dose Day 1 of the second JCAR015 infusion; Day 14 after the second JCAR015 infusion; and Day 28, Month 3, Month 6, and Month 12 after the last JCAR015 infusion
Population: The analysis population includes all enrolled subjects who underwent leukapheresis and had a sample that was evaluable for the assay.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| JCAR015 | Percentage of Participants Who Developed Anti-Therapeutic Antibodies Against JCAR015 | Day 28 after last infusion | 10 percentage of participants |
| JCAR015 | Percentage of Participants Who Developed Anti-Therapeutic Antibodies Against JCAR015 | Month 3 | 64 percentage of participants |
| JCAR015 | Percentage of Participants Who Developed Anti-Therapeutic Antibodies Against JCAR015 | Month 6 | 83 percentage of participants |
| JCAR015 | Percentage of Participants Who Developed Anti-Therapeutic Antibodies Against JCAR015 | Month 12 | 22 percentage of participants |
Secondary
Percentage of Participants With CR or CRi, as Determined by an IRC
ORR is defined as the percentage of participants with CR or CRi based on IRC assessment (refer to criteria in Outcome Measure #1)
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes participants with morphologic disease who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one JCAR015 infusion, and who were evaluable for response (excludes 5 subjects with Grade 5 brain edema who died within 8 days after JCAR015 infusion).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JCAR015 | Percentage of Participants With CR or CRi, as Determined by an IRC | 55.6 percentage of participants |
Secondary
Relapse-Free Survival (RFS), as Determined by an IRC
RFS is defined as the interval from the first documentation of CR or CRi (refer to Outcome Measure #1) to the earlier date of relapse or death due to any cause. Participants who proceeded to hematopoietic stem cell transplant (HSCT) after JCAR015 infusion were censored at the time of HSCT.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes participants with morphological disease at the time of the first JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone and at least one infusion of JCAR015, and who achieved a CR or CRi after JCAR015 infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | Relapse-Free Survival (RFS), as Determined by an IRC | 6.3 months |
Secondary
RFS, as Determined by an IRC
RFS is defined as the interval from the first documentation of CR or CRi (refer to Outcome Measure #1) to the earlier date of relapse or death due to any cause. Participants who proceeded to HSCT after JCAR015 infusion were censored at the time of HSCT.
Time frame: Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion
Population: The analysis population includes participants with morphologic disease at the time of JCAR015 infusion who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015, and who achieved a CR or CRi after JCAR015 infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | RFS, as Determined by an IRC | 4.4 months |
Secondary
Time to Maximum Concentration of JCAR015 (Tmax) in the Peripheral Blood as Measured by qPCR
Tmax is defined as the time after the JCAR015 infusion at which the maximum concentration (Cmax) as measured by qPCR is observed. If Cmax occurred after the second infusion, Tmax was calculated from the time of the second infusion.
Time frame: Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable)
Population: The analysis population includes all participants who received at least one infusion of JCAR015.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | Time to Maximum Concentration of JCAR015 (Tmax) in the Peripheral Blood as Measured by qPCR | 8 days |
Secondary
Tmax in the Peripheral Blood as Measured by Flow Cytometry
Tmax is defined as the time after the JCAR015 infusion at which the Cmax as measured by flow cytometry of the JCAR015 CAR is observed. If Cmax occurred after the second infusion, Tmax was calculated from the time of the second infusion.
Time frame: Pre-dose Day 1 of each JCAR015 infusion; Day 4, Day 7, Day 14, Day 21, and Day 28 after the first JCAR015 infusion until receipt of the second infusion; and Day 4, Day 7, Day 14, Day 21, and Day 28 after the second JCAR015 infusion (if applicable)
Population: The analysis population includes all participants who received at least one infusion of JCAR015 and whose Cmax was \>0.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| JCAR015 | Tmax in the Peripheral Blood as Measured by Flow Cytometry | 10.5 days |