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Study Evaluating the Efficacy and Safety of JCAR015 in Adult B-cell Acute Lymphoblastic Leukemia (B-ALL) (ROCKET)

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ClinicalTrials.gov Identifier: NCT02535364
Recruitment Status : Terminated (Safety reasons)
First Posted : August 28, 2015
Results First Posted : July 19, 2018
Last Update Posted : May 4, 2020
Sponsor:
Information provided by (Responsible Party):
Juno Therapeutics, a Subsidiary of Celgene

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Lymphoblastic Leukemia
Intervention Biological: JCAR015 (CD19-targeted CAR T cells)
Enrollment 82
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).
Arm/Group Title JCAR015
Hide 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
Reason Not Completed
Failure to meet criteria for Part A             22
Study placed on clinical hold by FDA             2
Disease progression             1
Period Title: Part B Screening
Started 57
Completed 40
Not Completed 17
Reason Not Completed
Study placed on clinical hold by FDA             7
Unable to manufacture JCAR015             3
Death             2
Physician Decision             1
Withdrawal by Subject             1
Adverse Event             1
Change in diagnosis, no longer eligible             2
Period Title: Study Treatment
Started 40
Completed 38
Not Completed 2
Reason Not Completed
Death             1
Study placed on clinical hold by FDA             1
Period Title: 12-Month Follow-up Period
Started 38
Completed 3
Not Completed 35
Reason Not Completed
Disease progression             22
Death             5
Underwent stem cell transplant             5
Subject received alternative therapy             2
Subject transferred to hospice             1
Arm/Group Title JCAR015
Hide Arm/Group Description Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Baseline Participants 38
Hide Baseline Analysis Population Description
Total number of subjects who received at least one infusion of JCAR015
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 38 participants
39
(19 to 69)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
39 or younger
19
  50.0%
40 to 64
15
  39.5%
65 or older
4
  10.5%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
Female
10
  26.3%
Male
28
  73.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
Hispanic or Latino
7
  18.4%
Not Hispanic or Latino
31
  81.6%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
   5.3%
Native Hawaiian or Other Pacific Islander
1
   2.6%
Black or African American
0
   0.0%
White
35
  92.1%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Time Since Diagnosis  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 38 participants
1.8
(1 to 22)
Number of Prior Lines of Therapy  
Median (Full Range)
Unit of measure:  Lines of therapy
Number Analyzed 38 participants
2
(1 to 7)
Most Recent Prior Regimen  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
Remission
8
  21.1%
No response
27
  71.1%
Not applicable
2
   5.3%
Missing
1
   2.6%
Prior Stem Cell Transplant  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 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   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
0
3
   7.9%
1
29
  76.3%
2
5
  13.2%
3
1
   2.6%
[1]
Measure Description:

0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair

From Oken MM, et al. Am J Clin Oncol 1982;5(6):649-655.

Philadelphia Chromosome Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
Philadelphia chromosome negative
34
  89.5%
Philadelphia chromosome positive
4
  10.5%
[1]
Measure Description: The Philadelphia (Ph) chromosome is an abnormally short chromosome 22 that results from translocation between the BCR gene on chromosome 22 with the ABL gene on chromosome 9. The resulting BCR-ABL gene encodes a fusion protein with uncontrolled tyrosine kinase activity and has been linked to chronic myeloid leukemia and one form of ALL.
1.Primary Outcome
Title Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematopoietic Recovery (CRi), as Determined by an Independent Review Committee (IRC)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
45.5
(24.4 to 67.8)
2.Secondary Outcome
Title Percentage of Participants With CR or CRi, as Determined by an IRC
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
55.6
(35.3 to 74.5)
3.Secondary Outcome
Title Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of participants
CR 8.3
CRi 33.3
4.Secondary Outcome
Title Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 32
Measure Type: Number
Unit of Measure: percentage of participants
CR 12.5
CRi 34.3
5.Secondary Outcome
Title Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of participants
MRD-negative CR/CRi 41.7
MRD-positive CR/CRi 0
MRD-negative CR/CRi unconfirmed 12.6
MRD-positive CR/CRi unconfirmed 4.2
6.Secondary Outcome
Title Percentage of Participants Who Achieved a MRD-Negative CR or CRi
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 32
Measure Type: Number
Unit of Measure: percentage of participants
MRD-negative CR/CRi 46.9
MRD-positive CR/CRi 0
MRD-negative CR/CRi unconfirmed 9.4
MRD-positive CR/CRi unconfirmed 3.1
7.Secondary Outcome
Title Relapse-Free Survival (RFS), as Determined by an IRC
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 10
Median (95% Confidence Interval)
Unit of Measure: months
6.3 [1] 
(1.9 to NA)
[1]
The upper limit of the 95% confidence interval was not reached.
8.Secondary Outcome
Title RFS, as Determined by an IRC
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: months
4.4
(2.1 to 9.4)
9.Secondary Outcome
Title Event-Free Survival (EFS)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 24
Median (95% Confidence Interval)
Unit of Measure: months
0.03
(0.03 to 3.8)
10.Secondary Outcome
Title EFS
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 38
Median (95% Confidence Interval)
Unit of Measure: months
2.7
(0.03 to 4.2)
11.Secondary Outcome
Title Overall Survival (OS)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 24
Median (95% Confidence Interval)
Unit of Measure: months
7.33
(5.16 to 12.68)
12.Secondary Outcome
Title OS
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 38
Median (95% Confidence Interval)
Unit of Measure: months
8.15
(5.32 to 12.68)
13.Secondary Outcome
Title Duration of Remission (DOR) as Determined by an IRC
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: months
4.4
(2.1 to 9.4)
14.Secondary Outcome
Title Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC, at Month 6 After the Final JCAR015 Infusion
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 32
Measure Type: Number
Unit of Measure: percentage of participants
Maintained CR at Month 6 11.1
Maintained CRi at Month 6 3.7
15.Secondary Outcome
Title Percentage of Participants Who Achieved a Morphologic Remission Within 6 Months After the Final JCAR015 Infusion and Then Proceeded to HSCT
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
11.1
(2.4 to 29.2)
16.Secondary Outcome
Title Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Quantitative Polymerase Chain Reaction (qPCR)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes all participants who received at least one infusion of JCAR015.
Arm/Group Title JCAR015
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 38
Median (Full Range)
Unit of Measure: vector copy number/microgram
69246
(32 to 408583)
17.Secondary Outcome
Title Maximum Concentration of JCAR015 (Cmax) in the Peripheral Blood by Flow Cytometry
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes all participants who received at least one infusion of JCAR015.
Arm/Group Title JCAR015
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 38
Median (Full Range)
Unit of Measure: cells/microliter
8.1
(0 to 556)
18.Secondary Outcome
Title Time to Maximum Concentration of JCAR015 (Tmax) in the Peripheral Blood as Measured by qPCR
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes all participants who received at least one infusion of JCAR015.
Arm/Group Title JCAR015
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 38
Median (Full Range)
Unit of Measure: days
8
(4 to 18)
19.Secondary Outcome
Title Tmax in the Peripheral Blood as Measured by Flow Cytometry
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 34
Median (Full Range)
Unit of Measure: days
10.5
(6 to 29)
20.Secondary Outcome
Title Area Under the Concentration-vs-Time Curve (AUC) for JCAR015 in the Peripheral Blood as Measured by qPCR
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes all participants who received at least one infusion of JCAR015.
Arm/Group Title JCAR015
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 38
Median (Full Range)
Unit of Measure: vector copy number*days/microgram
556520
(96 to 4628485)
21.Secondary Outcome
Title AUC for JCAR015 in the Peripheral Blood as Measured by Flow Cytometry
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes all participants who received at least one infusion of JCAR015.
Arm/Group Title JCAR015
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 38
Median (Full Range)
Unit of Measure: cells*days/microliter
60.6
(0 to 6806)
22.Secondary Outcome
Title Percentage of Participants Who Developed Anti-Therapeutic Antibodies Against JCAR015
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received up to two IV infusions of JCAR015 separated by 14 to 28 days.
Overall Number of Participants Analyzed 41
Measure Type: Number
Unit of Measure: percentage of participants
Day 28 after last infusion Number Analyzed 21 participants
10
Month 3 Number Analyzed 14 participants
64
Month 6 Number Analyzed 6 participants
83
Month 12 Number Analyzed 9 participants
22
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
Hide 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 (%)
Total   24/38 (63.16%) 
Hide Serious Adverse Events
JCAR015
Affected / at Risk (%)
Total   23/38 (60.53%) 
Blood and lymphatic system disorders   
Febrile neutropenia * 1  1/38 (2.63%) 
Cardiac disorders   
Atrial fibrillation * 1  1/38 (2.63%) 
Myocardial infarction * 1  1/38 (2.63%) 
Gastrointestinal disorders   
Neutropenic colitis * 1  1/38 (2.63%) 
Abdominal pain * 1  1/38 (2.63%) 
General disorders   
Asthenia * 1  1/38 (2.63%) 
Pyrexia * 1  1/38 (2.63%) 
Hepatobiliary disorders   
Cholecystitis * 1  1/38 (2.63%) 
Immune system disorders   
Cytokine release syndrome * 1  8/38 (21.05%) 
Infections and infestations   
Sepsis * 1  2/38 (5.26%) 
Bacteraemia * 1  1/38 (2.63%) 
Fungaemia * 1  1/38 (2.63%) 
Nervous system disorders   
Encephalopathy * 1  8/38 (21.05%) 
Brain oedema * 1  5/38 (13.16%) 
Seizure * 1  2/38 (5.26%) 
Generalised tonic-clonic seizure * 1  1/38 (2.63%) 
1
Term from vocabulary, MedDRA (18.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
JCAR015
Affected / at Risk (%)
Total   38/38 (100.00%) 
Blood and lymphatic system disorders   
Anaemia * 1  9/38 (23.68%) 
Febrile neutropenia * 1  6/38 (15.79%) 
Neutropenia * 1  3/38 (7.89%) 
Cardiac disorders   
Sinus bradycardia * 1  3/38 (7.89%) 
Angina pectoris * 1  2/38 (5.26%) 
Bradycardia * 1  2/38 (5.26%) 
Tachycardia * 1  2/38 (5.26%) 
Ear and labyrinth disorders   
Ear pain * 1  2/38 (5.26%) 
Eye disorders   
Photophobia * 1  3/38 (7.89%) 
Gastrointestinal disorders   
Diarrhoea * 1  17/38 (44.74%) 
Nausea * 1  16/38 (42.11%) 
Vomiting * 1  15/38 (39.47%) 
Constipation * 1  5/38 (13.16%) 
Abdominal pain * 1  4/38 (10.53%) 
Abdominal distension * 1  3/38 (7.89%) 
Abdominal discomfort * 1  2/38 (5.26%) 
Abdominal pain lower * 1  2/38 (5.26%) 
Abdominal pain upper * 1  2/38 (5.26%) 
Dry mouth * 1  2/38 (5.26%) 
Dyspepsia * 1  2/38 (5.26%) 
Dysphagia * 1  2/38 (5.26%) 
Faecal incontinence * 1  2/38 (5.26%) 
Haemorrhoids * 1  2/38 (5.26%) 
Retching * 1  2/38 (5.26%) 
General disorders   
Fatigue * 1  9/38 (23.68%) 
Chills * 1  7/38 (18.42%) 
Oedema peripheral * 1  7/38 (18.42%) 
Asthenia * 1  6/38 (15.79%) 
Pyrexia * 1  5/38 (13.16%) 
Gait disturbance * 1  4/38 (10.53%) 
Pain * 1  3/38 (7.89%) 
Catheter site pain * 1  2/38 (5.26%) 
Chest discomfort * 1  2/38 (5.26%) 
Malaise * 1  2/38 (5.26%) 
Mucosal inflammation * 1  2/38 (5.26%) 
Peripheral swelling * 1  2/38 (5.26%) 
Immune system disorders   
Cytokine release syndrome * 1  29/38 (76.32%) 
Infections and infestations   
Pneumonia * 1  4/38 (10.53%) 
Staphylococcal infection * 1  4/38 (10.53%) 
Candida infection * 1  3/38 (7.89%) 
Cellulitis * 1  2/38 (5.26%) 
Injury, poisoning and procedural complications   
Fall * 1  4/38 (10.53%) 
Laceration * 1  2/38 (5.26%) 
Investigations   
Neutrophil count decreased * 1  7/38 (18.42%) 
Platelet count decreased * 1  7/38 (18.42%) 
White blood cell count decreased * 1  6/38 (15.79%) 
Blood bilirubin increased * 1  4/38 (10.53%) 
Alanine aminotransferase increased * 1  2/38 (5.26%) 
Blood alkaline phosphatase increased * 1  2/38 (5.26%) 
Blood bicarbonate decreased * 1  2/38 (5.26%) 
Blood creatinine increased * 1  2/38 (5.26%) 
Blood fibrinogen decreased * 1  2/38 (5.26%) 
International normalised ratio increased * 1  2/38 (5.26%) 
Lymphocyte count decreased * 1  2/38 (5.26%) 
Metabolism and nutrition disorders   
Hypokalaemia * 1  10/38 (26.32%) 
Decreased appetite * 1  8/38 (21.05%) 
Hypomagnesaemia * 1  8/38 (21.05%) 
Hypophosphataemia * 1  5/38 (13.16%) 
Fluid overload * 1  3/38 (7.89%) 
Hyponatraemia * 1  3/38 (7.89%) 
Hypernatraemia * 1  2/38 (5.26%) 
Hyperuricaemia * 1  2/38 (5.26%) 
Hypophagia * 1  2/38 (5.26%) 
Musculoskeletal and connective tissue disorders   
Muscular weakness * 1  8/38 (21.05%) 
Pain in extremity * 1  5/38 (13.16%) 
Back pain * 1  4/38 (10.53%) 
Arthralgia * 1  3/38 (7.89%) 
Myalgia * 1  3/38 (7.89%) 
Musculoskeletal pain * 1  2/38 (5.26%) 
Nervous system disorders   
Aphasia * 1  15/38 (39.47%) 
Tremor * 1  12/38 (31.58%) 
Headache * 1  10/38 (26.32%) 
Somnolence * 1  10/38 (26.32%) 
Lethargy * 1  8/38 (21.05%) 
Seizure * 1  7/38 (18.42%) 
Depressed level of consciousness * 1  6/38 (15.79%) 
Encephalopathy * 1  6/38 (15.79%) 
Dizziness * 1  4/38 (10.53%) 
Peripheral sensory neuropathy * 1  4/38 (10.53%) 
Hypoaesthesia * 1  3/38 (7.89%) 
Memory impairment * 1  3/38 (7.89%) 
Ataxia * 1  2/38 (5.26%) 
Migraine * 1  2/38 (5.26%) 
Myoclonus * 1  2/38 (5.26%) 
Neuropathy peripheral * 1  2/38 (5.26%) 
Paraesthesia * 1  2/38 (5.26%) 
Psychiatric disorders   
Confusional state * 1  18/38 (47.37%) 
Insomnia * 1  8/38 (21.05%) 
Agitation * 1  6/38 (15.79%) 
Delirium * 1  6/38 (15.79%) 
Anxiety * 1  5/38 (13.16%) 
Mental status changes * 1  4/38 (10.53%) 
Depression * 1  3/38 (7.89%) 
Hallucination * 1  3/38 (7.89%) 
Renal and urinary disorders   
Haematuria * 1  4/38 (10.53%) 
Urinary incontinence * 1  3/38 (7.89%) 
Urinary retention * 1  3/38 (7.89%) 
Acute kidney injury * 1  2/38 (5.26%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  5/38 (13.16%) 
Oedema * 1  4/38 (10.53%) 
Dyspnoea * 1  3/38 (7.89%) 
Hypoxia * 1  3/38 (7.89%) 
Pleural effusion * 1  3/38 (7.89%) 
Aspiration * 1  2/38 (5.26%) 
Hiccups * 1  2/38 (5.26%) 
Tachypnoea * 1  2/38 (5.26%) 
Skin and subcutaneous tissue disorders   
Pruritus * 1  4/38 (10.53%) 
Night sweats * 1  3/38 (7.89%) 
Alopecia * 1  2/38 (5.26%) 
Dry skin * 1  2/38 (5.26%) 
Rash pruritic * 1  2/38 (5.26%) 
Vascular disorders   
Hypertension * 1  6/38 (15.79%) 
Hypotension * 1  3/38 (7.89%) 
Deep vein thrombosis * 1  2/38 (5.26%) 
Haematoma * 1  2/38 (5.26%) 
1
Term from vocabulary, MedDRA (18.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Dr. Nikolaus Trede
Organization: Juno Therapeutics
Phone: 206-566-5886
EMail: Nick.Trede@junotherapeutics.com
Publications:
Layout table for additonal information
Responsible Party: Juno Therapeutics, a Subsidiary of Celgene
ClinicalTrials.gov Identifier: NCT02535364    
Other Study ID Numbers: 015001
First Submitted: August 24, 2015
First Posted: August 28, 2015
Results First Submitted: April 24, 2018
Results First Posted: July 19, 2018
Last Update Posted: May 4, 2020