ROCKET: Study Evaluating the Efficacy and Safety of JCAR015 in Adult B-cell Acute Lymphoblastic Leukemia (B-ALL)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: JCAR015 (CD19-targeted CAR T cells) JCAR015 was administered as two intravenous (IV) infusions separated by 14 to 28 days. |
Biological: JCAR015 (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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 [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 CR or CRi, as Determined by an IRC [Day 1 (first JCAR015 infusion) up to 12 months after the last JCAR015 infusion]
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.
- 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.
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥ 18 years at the time of consent
-
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
-
Morphological evidence of disease in bone marrow (at least 5% blasts)
-
Evidence of CD19 expression
-
Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2 at the time of screening
-
Adequate pulmonary, renal, hepatic, and cardiac function
-
Adequate central or peripheral vascular access for leukapheresis procedure
Exclusion Criteria:
-
Isolated extramedullary disease relapse
-
Concomitant genetic syndrome or other known bone marrow failure syndrome
-
Burkitt's lymphoma/leukemia or chronic myelogenous leukemia lymphoid blast crisis (p210 BCR-ABL+)
-
Prior malignancy, unless treated with curative intent and with no evidence of active disease present for > 5 years before screening
-
Prior treatment with any gene therapy product
-
Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
-
Systemic fungal, bacterial, viral, or other infection that is not controlled, at the time of screening
-
Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
-
Active central nervous system (CNS) involvement by malignancy (defined as CNS-3 per National Comprehensive Cancer Network [NCCN] guidelines)
-
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
-
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
-
Participation in an investigational research study using an investigational agent within 30 days of screening
-
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
-
Pregnant or nursing women
-
Use of prohibited medications:
-
Steroids: Therapeutic doses of corticosteroids are prohibited within 7 days prior to leukapheresis.
-
Allogeneic cellular therapy: Donor lymphocyte infusions (DLI) are prohibited within 4 weeks prior to leukapheresis
-
GVHD therapies: Any drug used for GVHD within 4 weeks prior to leukapheresis
-
Chemotherapies: Salvage chemotherapy must be stopped at least 1 week prior to leukapheresis
-
Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama Birmingham Comprehensive Cancer Center | Birmingham | Alabama | United States | 35295 |
| 2 | City of Hope | Duarte | California | United States | 91010 |
| 3 | University of California | San Francisco | California | United States | 94143 |
| 4 | University of Colorado Denver -- Anschutz Medical Campus | Aurora | Colorado | United States | 80045 |
| 5 | Sylvester Comprehensive Cancer Center/UMHC | Miami | Florida | United States | 33136 |
| 6 | The Blood and Marrow Transplant Program at Northside Hospital | Atlanta | Georgia | United States | 30342 |
| 7 | Northwestern University Robert H Lurie Comprehensive Cancer Center | Chicago | Illinois | United States | 60611 |
| 8 | University of Chicago Medical Center | Chicago | Illinois | United States | 60637 |
| 9 | Sidney Kimmel Comprehensive Cancer Center @ Johns Hopkins | Baltimore | Maryland | United States | 21287 |
| 10 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 11 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 12 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 13 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 14 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 15 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 16 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 17 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
| 18 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Juno Therapeutics, a Subsidiary of Celgene
Investigators
- Study Director: Nikolaus Trede, MD, PhD, Juno Therapeutics, Inc.
Study Documents (Full-Text)
More Information
Publications
- Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M, Borquez-Ojeda O, Qu J, Wasielewska T, He Q, Bernal Y, Rijo IV, Hedvat C, Kobos R, Curran K, Steinherz P, Jurcic J, Rosenblat T, Maslak P, Frattini M, Sadelain M. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013 Mar 20;5(177):177ra38. doi: 10.1126/scitranslmed.3005930.
- Brentjens RJ, Rivière I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O, Olszewska M, Bernal Y, Pegram H, Przybylowski M, Hollyman D, Usachenko Y, Pirraglia D, Hosey J, Santos E, Halton E, Maslak P, Scheinberg D, Jurcic J, Heaney M, Heller G, Frattini M, Sadelain M. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011 Nov 3;118(18):4817-28. doi: 10.1182/blood-2011-04-348540. Epub 2011 Aug 17.
- Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SS, Stefanski J, Borquez-Ojeda O, Olszewska M, Qu J, Wasielewska T, He Q, Fink M, Shinglot H, Youssif M, Satter M, Wang Y, Hosey J, Quintanilla H, Halton E, Bernal Y, Bouhassira DC, Arcila ME, Gonen M, Roboz GJ, Maslak P, Douer D, Frattini MG, Giralt S, Sadelain M, Brentjens R. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014 Feb 19;6(224):224ra25. doi: 10.1126/scitranslmed.3008226.
- Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013 Apr;3(4):388-98. doi: 10.1158/2159-8290.CD-12-0548. Epub 2013 Apr 2. Review.
- 015001
Study Results
Participant Flow
| Recruitment Details | A total of 82 participants were enrolled at 15 study centers within the United States. |
|---|---|
| Pre-assignment Detail | Participants were adults with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (ALL). |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two intravenous (IV) infusions of JCAR015 separated by 14 to 28 days. In Part A, participants received at the Investigator's discretion, cytoreductive chemotherapy based on the Investigator's choice and/or supportive care. In Part B, eligible participants received two IV doses of JCAR015 CAR T cells. JCAR015 infusion was preceded by lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine. |
| Period Title: Part A Screening Through Leukapheresis | |
| STARTED | 82 |
| COMPLETED | 57 |
| NOT COMPLETED | 25 |
| Period Title: Part A Screening Through Leukapheresis | |
| STARTED | 57 |
| COMPLETED | 40 |
| NOT COMPLETED | 17 |
| Period Title: Part A Screening Through Leukapheresis | |
| STARTED | 40 |
| COMPLETED | 38 |
| NOT COMPLETED | 2 |
| Period Title: Part A Screening Through Leukapheresis | |
| STARTED | 38 |
| COMPLETED | 3 |
| NOT COMPLETED | 35 |
Baseline Characteristics
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Overall Participants | 38 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
39
|
| Age, Customized (Count of Participants) | |
| 39 or younger |
19
50%
|
| 40 to 64 |
15
39.5%
|
| 65 or older |
4
10.5%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
10
26.3%
|
| Male |
28
73.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
7
18.4%
|
| Not Hispanic or Latino |
31
81.6%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
2
5.3%
|
| Native Hawaiian or Other Pacific Islander |
1
2.6%
|
| Black or African American |
0
0%
|
| White |
35
92.1%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Time Since Diagnosis (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
1.8
|
| Number of Prior Lines of Therapy (lines of therapy) [Median (Full Range) ] | |
| Median (Full Range) [lines of therapy] |
2
|
| Most Recent Prior Regimen (Count of Participants) | |
| Blinatumomab monotherapy |
11
28.9%
|
| Investigational agent |
1
2.6%
|
| Marqibo |
2
5.3%
|
| Multi-agent chemotherapy |
15
39.5%
|
| Tyrosine kinase inhibitor + chemotherapy |
2
5.3%
|
| Tyrosine kinase inhibitor alone |
1
2.6%
|
| Other |
6
15.8%
|
| Response to Most Recent Prior Regimen (Count of Participants) | |
| Remission |
8
21.1%
|
| No response |
27
71.1%
|
| Not applicable |
2
5.3%
|
| Missing |
1
2.6%
|
| Prior Stem Cell Transplant (Count of Participants) | |
| Received prior stem cell transplant |
14
36.8%
|
| Did not receive prior stem cell transplant |
24
63.2%
|
| Eastern Cooperative Oncology Group (ECOG) Score (Count of Participants) | |
| 0 |
3
7.9%
|
| 1 |
29
76.3%
|
| 2 |
5
13.2%
|
| 3 |
1
2.6%
|
| Philadelphia Chromosome Status (Count of Participants) | |
| Philadelphia chromosome negative |
34
89.5%
|
| Philadelphia chromosome positive |
4
10.5%
|
Outcome Measures
| Title | Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematopoietic Recovery (CRi), as Determined by an Independent Review Committee (IRC) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 22 |
| Number (95% Confidence Interval) [percentage of participants] |
45.5
119.7%
|
| Title | Percentage of Participants With CR or CRi, as Determined by an IRC |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 27 |
| Number (95% Confidence Interval) [percentage of participants] |
55.6
146.3%
|
| Title | Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 24 |
| CR |
8.3
21.8%
|
| CRi |
33.3
87.6%
|
| Title | Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 32 |
| CR |
12.5
32.9%
|
| CRi |
34.3
90.3%
|
| Title | Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 24 |
| MRD-negative CR/CRi |
41.7
109.7%
|
| MRD-positive CR/CRi |
0
0%
|
| MRD-negative CR/CRi unconfirmed |
12.6
33.2%
|
| MRD-positive CR/CRi unconfirmed |
4.2
11.1%
|
| Title | Percentage of Participants Who Achieved a MRD-Negative CR or CRi |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 32 |
| MRD-negative CR/CRi |
46.9
123.4%
|
| MRD-positive CR/CRi |
0
0%
|
| MRD-negative CR/CRi unconfirmed |
9.4
24.7%
|
| MRD-positive CR/CRi unconfirmed |
3.1
8.2%
|
| Title | Relapse-Free Survival (RFS), as Determined by an IRC |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 10 |
| Median (95% Confidence Interval) [months] |
6.3
|
| Title | RFS, as Determined by an IRC |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 15 |
| Median (95% Confidence Interval) [months] |
4.4
|
| Title | Event-Free Survival (EFS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 24 |
| Median (95% Confidence Interval) [months] |
0.03
|
| Title | EFS |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all participants who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 38 |
| Median (95% Confidence Interval) [months] |
2.7
|
| Title | Overall Survival (OS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 24 |
| Median (95% Confidence Interval) [months] |
7.33
|
| Title | OS |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all participants who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 38 |
| Median (95% Confidence Interval) [months] |
8.15
|
| Title | Duration of Remission (DOR) as Determined by an IRC |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 15 |
| Median (95% Confidence Interval) [months] |
4.4
|
| Title | Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC, at Month 6 After the Final JCAR015 Infusion |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all participants who received lymphodepleting chemotherapy with cyclophosphamide alone or cyclophosphamide + fludarabine and at least one infusion of JCAR015. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 32 |
| Maintained CR at Month 6 |
11.1
29.2%
|
| Maintained CRi at Month 6 |
3.7
9.7%
|
| Title | Percentage of Participants Who Achieved a Morphologic Remission Within 6 Months After the Final JCAR015 Infusion and Then Proceeded to HSCT |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 27 |
| Number (95% Confidence Interval) [percentage of participants] |
11.1
29.2%
|
| Title | Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Quantitative Polymerase Chain Reaction (qPCR) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all participants who received at least one infusion of JCAR015. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 38 |
| Median (Full Range) [vector copy number/microgram] |
69246
|
| Title | Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Flow Cytometry |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all participants who received at least one infusion of JCAR015. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 38 |
| Median (Full Range) [cells/microliter] |
8.1
|
| Title | Time to Maximum Concentration of JCAR015 (Tmax) in the Peripheral Blood as Measured by qPCR |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all participants who received at least one infusion of JCAR015. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 38 |
| Median (Full Range) [days] |
8
|
| Title | Tmax in the Peripheral Blood as Measured by Flow Cytometry |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all participants who received at least one infusion of JCAR015 and whose Cmax was >0. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 34 |
| Median (Full Range) [days] |
10.5
|
| Title | Area Under the Concentration-vs-Time Curve (AUC) for JCAR015 in the Peripheral Blood as Measured by qPCR |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all participants who received at least one infusion of JCAR015. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 38 |
| Median (Full Range) [vector copy number*days/microgram] |
556520
|
| Title | AUC for JCAR015 in the Peripheral Blood as Measured by Flow Cytometry |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all participants who received at least one infusion of JCAR015. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 38 |
| Median (Full Range) [cells*days/microliter] |
60.6
|
| Title | Percentage of Participants Who Developed Anti-Therapeutic Antibodies Against JCAR015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all enrolled subjects who underwent leukapheresis and had a sample that was evaluable for the assay. |
| Arm/Group Title | JCAR015 |
|---|---|
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. |
| Measure Participants | 41 |
| Day 28 after last infusion |
10
26.3%
|
| Month 3 |
64
168.4%
|
| Month 6 |
83
218.4%
|
| Month 12 |
22
57.9%
|
Adverse Events
| Time Frame | From the time of the first JCAR015 infusion up to 12 months after the last JCAR015 infusion | |
|---|---|---|
| Adverse Event Reporting Description | The summary tables include treatment-emergent adverse events, defined as adverse events that (1) occurred or worsened after the first JCAR015 infusion and up to 30 days after the final JCAR015 infusion or (2) led to JCAR015 discontinuation. Adverse events occurring after the initiation of another anticancer therapy were not considered as treatment-emergent adverse events. | |
| Arm/Group Title | JCAR015 | |
| Arm/Group Description | Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days. | |
All Cause Mortality |
||
| JCAR015 | ||
| Affected / at Risk (%) | # Events | |
| Total | 24/38 (63.2%) | |
Serious Adverse Events |
||
| JCAR015 | ||
| Affected / at Risk (%) | # Events | |
| Total | 23/38 (60.5%) | |
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 1/38 (2.6%) | |
| Cardiac disorders | ||
| Atrial fibrillation | 1/38 (2.6%) | |
| Myocardial infarction | 1/38 (2.6%) | |
| Gastrointestinal disorders | ||
| Neutropenic colitis | 1/38 (2.6%) | |
| Abdominal pain | 1/38 (2.6%) | |
| General disorders | ||
| Asthenia | 1/38 (2.6%) | |
| Pyrexia | 1/38 (2.6%) | |
| Hepatobiliary disorders | ||
| Cholecystitis | 1/38 (2.6%) | |
| Immune system disorders | ||
| Cytokine release syndrome | 8/38 (21.1%) | |
| Infections and infestations | ||
| Sepsis | 2/38 (5.3%) | |
| Bacteraemia | 1/38 (2.6%) | |
| Fungaemia | 1/38 (2.6%) | |
| Nervous system disorders | ||
| Encephalopathy | 8/38 (21.1%) | |
| Brain oedema | 5/38 (13.2%) | |
| Seizure | 2/38 (5.3%) | |
| Generalised tonic-clonic seizure | 1/38 (2.6%) | |
Other (Not Including Serious) Adverse Events |
||
| JCAR015 | ||
| Affected / at Risk (%) | # Events | |
| Total | 38/38 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 9/38 (23.7%) | |
| Febrile neutropenia | 6/38 (15.8%) | |
| Neutropenia | 3/38 (7.9%) | |
| Cardiac disorders | ||
| Sinus bradycardia | 3/38 (7.9%) | |
| Angina pectoris | 2/38 (5.3%) | |
| Bradycardia | 2/38 (5.3%) | |
| Tachycardia | 2/38 (5.3%) | |
| Ear and labyrinth disorders | ||
| Ear pain | 2/38 (5.3%) | |
| Eye disorders | ||
| Photophobia | 3/38 (7.9%) | |
| Gastrointestinal disorders | ||
| Diarrhoea | 17/38 (44.7%) | |
| Nausea | 16/38 (42.1%) | |
| Vomiting | 15/38 (39.5%) | |
| Constipation | 5/38 (13.2%) | |
| Abdominal pain | 4/38 (10.5%) | |
| Abdominal distension | 3/38 (7.9%) | |
| Abdominal discomfort | 2/38 (5.3%) | |
| Abdominal pain lower | 2/38 (5.3%) | |
| Abdominal pain upper | 2/38 (5.3%) | |
| Dry mouth | 2/38 (5.3%) | |
| Dyspepsia | 2/38 (5.3%) | |
| Dysphagia | 2/38 (5.3%) | |
| Faecal incontinence | 2/38 (5.3%) | |
| Haemorrhoids | 2/38 (5.3%) | |
| Retching | 2/38 (5.3%) | |
| General disorders | ||
| Fatigue | 9/38 (23.7%) | |
| Chills | 7/38 (18.4%) | |
| Oedema peripheral | 7/38 (18.4%) | |
| Asthenia | 6/38 (15.8%) | |
| Pyrexia | 5/38 (13.2%) | |
| Gait disturbance | 4/38 (10.5%) | |
| Pain | 3/38 (7.9%) | |
| Catheter site pain | 2/38 (5.3%) | |
| Chest discomfort | 2/38 (5.3%) | |
| Malaise | 2/38 (5.3%) | |
| Mucosal inflammation | 2/38 (5.3%) | |
| Peripheral swelling | 2/38 (5.3%) | |
| Immune system disorders | ||
| Cytokine release syndrome | 29/38 (76.3%) | |
| Infections and infestations | ||
| Pneumonia | 4/38 (10.5%) | |
| Staphylococcal infection | 4/38 (10.5%) | |
| Candida infection | 3/38 (7.9%) | |
| Cellulitis | 2/38 (5.3%) | |
| Injury, poisoning and procedural complications | ||
| Fall | 4/38 (10.5%) | |
| Laceration | 2/38 (5.3%) | |
| Investigations | ||
| Neutrophil count decreased | 7/38 (18.4%) | |
| Platelet count decreased | 7/38 (18.4%) | |
| White blood cell count decreased | 6/38 (15.8%) | |
| Blood bilirubin increased | 4/38 (10.5%) | |
| Alanine aminotransferase increased | 2/38 (5.3%) | |
| Blood alkaline phosphatase increased | 2/38 (5.3%) | |
| Blood bicarbonate decreased | 2/38 (5.3%) | |
| Blood creatinine increased | 2/38 (5.3%) | |
| Blood fibrinogen decreased | 2/38 (5.3%) | |
| International normalised ratio increased | 2/38 (5.3%) | |
| Lymphocyte count decreased | 2/38 (5.3%) | |
| Metabolism and nutrition disorders | ||
| Hypokalaemia | 10/38 (26.3%) | |
| Decreased appetite | 8/38 (21.1%) | |
| Hypomagnesaemia | 8/38 (21.1%) | |
| Hypophosphataemia | 5/38 (13.2%) | |
| Fluid overload | 3/38 (7.9%) | |
| Hyponatraemia | 3/38 (7.9%) | |
| Hypernatraemia | 2/38 (5.3%) | |
| Hyperuricaemia | 2/38 (5.3%) | |
| Hypophagia | 2/38 (5.3%) | |
| Musculoskeletal and connective tissue disorders | ||
| Muscular weakness | 8/38 (21.1%) | |
| Pain in extremity | 5/38 (13.2%) | |
| Back pain | 4/38 (10.5%) | |
| Arthralgia | 3/38 (7.9%) | |
| Myalgia | 3/38 (7.9%) | |
| Musculoskeletal pain | 2/38 (5.3%) | |
| Nervous system disorders | ||
| Aphasia | 15/38 (39.5%) | |
| Tremor | 12/38 (31.6%) | |
| Headache | 10/38 (26.3%) | |
| Somnolence | 10/38 (26.3%) | |
| Lethargy | 8/38 (21.1%) | |
| Seizure | 7/38 (18.4%) | |
| Depressed level of consciousness | 6/38 (15.8%) | |
| Encephalopathy | 6/38 (15.8%) | |
| Dizziness | 4/38 (10.5%) | |
| Peripheral sensory neuropathy | 4/38 (10.5%) | |
| Hypoaesthesia | 3/38 (7.9%) | |
| Memory impairment | 3/38 (7.9%) | |
| Ataxia | 2/38 (5.3%) | |
| Migraine | 2/38 (5.3%) | |
| Myoclonus | 2/38 (5.3%) | |
| Neuropathy peripheral | 2/38 (5.3%) | |
| Paraesthesia | 2/38 (5.3%) | |
| Psychiatric disorders | ||
| Confusional state | 18/38 (47.4%) | |
| Insomnia | 8/38 (21.1%) | |
| Agitation | 6/38 (15.8%) | |
| Delirium | 6/38 (15.8%) | |
| Anxiety | 5/38 (13.2%) | |
| Mental status changes | 4/38 (10.5%) | |
| Depression | 3/38 (7.9%) | |
| Hallucination | 3/38 (7.9%) | |
| Renal and urinary disorders | ||
| Haematuria | 4/38 (10.5%) | |
| Urinary incontinence | 3/38 (7.9%) | |
| Urinary retention | 3/38 (7.9%) | |
| Acute kidney injury | 2/38 (5.3%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 5/38 (13.2%) | |
| Oedema | 4/38 (10.5%) | |
| Dyspnoea | 3/38 (7.9%) | |
| Hypoxia | 3/38 (7.9%) | |
| Pleural effusion | 3/38 (7.9%) | |
| Aspiration | 2/38 (5.3%) | |
| Hiccups | 2/38 (5.3%) | |
| Tachypnoea | 2/38 (5.3%) | |
| Skin and subcutaneous tissue disorders | ||
| Pruritus | 4/38 (10.5%) | |
| Night sweats | 3/38 (7.9%) | |
| Alopecia | 2/38 (5.3%) | |
| Dry skin | 2/38 (5.3%) | |
| Rash pruritic | 2/38 (5.3%) | |
| Vascular disorders | ||
| Hypertension | 6/38 (15.8%) | |
| Hypotension | 3/38 (7.9%) | |
| Deep vein thrombosis | 2/38 (5.3%) | |
| Haematoma | 2/38 (5.3%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Investigators have the right to publish and/or present study data after publication of the sponsor's multicenter study publication provided that the investigator shall (i) provide the sponsor a copy of any proposed publication or presentation generally thirty (30) days in advance of the submission; (ii) delete any confidential information of the sponsor; and (iii) delay submission for generally up to ninety (90) days to permit the sponsor to prepare and file intellectual property applications.
Results Point of Contact
| Name/Title | Dr. Nikolaus Trede |
|---|---|
| Organization | Juno Therapeutics |
| Phone | 206-566-5886 |
| Nick.Trede@junotherapeutics.com |
- 015001