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NCT02535364: ROCKET

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

Terminated Phase 2 Results posted Last updated 4 May 2020
What this trial tests

Phase 2 trial testing JCAR015 (CD19-targeted CAR T cells) in Acute Lymphoblastic Leukemia in 82 participants. Terminated before completion.

Timeline
21 August 2015
Primary endpoint
24 April 2017
1 September 2017

Quick facts

Lead sponsorJuno Therapeutics, a Subsidiary of Celgene
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment82
Start date21 August 2015
Primary completion24 April 2017
Estimated completion1 September 2017
Sites18 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Juno Therapeutics, a Subsidiary of Celgene — full company profile →

Who can join

18 and older, any sex, with Acute Lymphoblastic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematopoietic Recovery (CRi), as Determined by an Independent Review Committee (IRC) Primary · 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 ev

GroupValue95% CI
JCAR01545.524.4 – 67.8
Percentage of Participants With CR or CRi, as Determined by an IRC Secondary · 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)

GroupValue95% CI
JCAR01555.635.3 – 74.5
Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC Secondary · 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).

CR
GroupValue95% CI
JCAR0158.3
CRi
GroupValue95% CI
JCAR01533.3
Percentage of Participants Who Achieved a CR or CRi, as Determined by an IRC Secondary · 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).

CR
GroupValue95% CI
JCAR01512.5
CRi
GroupValue95% CI
JCAR01534.3
Percentage of Participants Who Achieved a Minimal Residual Disease (MRD)-Negative CR or CRi Secondary · 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.

MRD-negative CR/CRi
GroupValue95% CI
JCAR01541.7
MRD-positive CR/CRi
GroupValue95% CI
JCAR0150
MRD-negative CR/CRi unconfirmed
GroupValue95% CI
JCAR01512.6
MRD-positive CR/CRi unconfirmed
GroupValue95% CI
JCAR0154.2
Percentage of Participants Who Achieved a MRD-Negative CR or CRi Secondary · 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.

MRD-negative CR/CRi
GroupValue95% CI
JCAR01546.9
MRD-positive CR/CRi
GroupValue95% CI
JCAR0150
MRD-negative CR/CRi unconfirmed
GroupValue95% CI
JCAR0159.4
MRD-positive CR/CRi unconfirmed
GroupValue95% CI
JCAR0153.1
Relapse-Free Survival (RFS), as Determined by an IRC Secondary · 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.

GroupValue95% CI
JCAR0156.31.9 – NA
RFS, as Determined by an IRC Secondary · 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.

GroupValue95% CI
JCAR0154.42.1 – 9.4
Event-Free Survival (EFS) Secondary · 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.

GroupValue95% CI
JCAR0150.030.03 – 3.8
EFS Secondary · 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.

GroupValue95% CI
JCAR0152.70.03 – 4.2
Overall Survival (OS) Secondary · 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.

GroupValue95% CI
JCAR0157.335.16 – 12.68
OS Secondary · 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.

GroupValue95% CI
JCAR0158.155.32 – 12.68

Adverse events — posted to ClinicalTrials.gov

Time frame: From the time of the first JCAR015 infusion up to 12 months after the last JCAR015 infusion. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

JCAR015
Serious: 23/38 (61%)
Deaths: 24/38

Serious adverse events (16 terms)

ReactionSystemJCAR015
EncephalopathyNervous system disorders
Cytokine release syndromeImmune system disorders
Brain oedemaNervous system disorders
SeizureNervous system disorders
SepsisInfections and infestations
Generalised tonic-clonic seizureNervous system disorders
BacteraemiaInfections and infestations
FungaemiaInfections and infestations
Neutropenic colitisGastrointestinal disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Myocardial infarctionCardiac disorders
CholecystitisHepatobiliary disorders
Abdominal painGastrointestinal disorders
Other adverse events (115 terms — click to expand)

ReactionSystemJCAR015
Cytokine release syndromeImmune system disorders
Confusional statePsychiatric disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
AphasiaNervous system disorders
VomitingGastrointestinal disorders
TremorNervous system disorders
HeadacheNervous system disorders
HypokalaemiaMetabolism and nutrition disorders
SomnolenceNervous system disorders
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
LethargyNervous system disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
ChillsGeneral disorders
Neutrophil count decreasedInvestigations
Oedema peripheralGeneral disorders
Platelet count decreasedInvestigations
SeizureNervous system disorders
AgitationPsychiatric disorders
AstheniaGeneral disorders
DeliriumPsychiatric disorders
Depressed level of consciousnessNervous system disorders
EncephalopathyNervous system disorders
Febrile neutropeniaBlood and lymphatic system disorders
HypertensionVascular disorders
White blood cell count decreasedInvestigations
AnxietyPsychiatric disorders
ConstipationGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
HypophosphataemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
Abdominal painGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
Blood bilirubin increasedInvestigations
DizzinessNervous system disorders

Most-reported serious reactions: Encephalopathy, Cytokine release syndrome, Brain oedema, Seizure, Sepsis, Generalised tonic-clonic seizure, Bacteraemia, Fungaemia.

Data from ClinicalTrials.gov NCT02535364 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Engineered T cells: the promise and challenges of cancer immunotherapy.
    Fesnak AD, June CH, Levine BL. · · 2016 · cited 812× · PMID 27550819 · DOI 10.1038/nrc.2016.97
  2. Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts.
    Hartmann J, Schüßler-Lenz M, Bondanza A, Buchholz CJ. · · 2017 · cited 353× · PMID 28765140 · DOI 10.15252/emmm.201607485
  3. Cornerstones of CRISPR-Cas in drug discovery and therapy.
    Fellmann C, Gowen BG, Lin PC, Doudna JA, et al · · 2017 · cited 340× · PMID 28008168 · DOI 10.1038/nrd.2016.238
  4. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events.
    Maus MV, Alexander S, Bishop MR, Brudno JN, et al · · 2020 · cited 211× · PMID 33335028 · DOI 10.1136/jitc-2020-001511
  5. Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL.
    Sheth VS, Gauthier J. · · 2021 · cited 179× · PMID 33230186 · DOI 10.1038/s41409-020-01134-4
  6. Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany.
    Albinger N, Hartmann J, Ullrich E. · · 2021 · cited 171× · PMID 33753909 · DOI 10.1038/s41434-021-00246-w
  7. The biological basis and clinical symptoms of CAR-T therapy-associated toxicites.
    Titov A, Petukhov A, Staliarova A, Motorin D, et al · · 2018 · cited 91× · PMID 30181581 · DOI 10.1038/s41419-018-0918-x
  8. A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies.
    Razeghian E, Nasution MKM, Rahman HS, Gardanova ZR, et al · · 2021 · cited 80× · PMID 34321099 · DOI 10.1186/s13287-021-02510-7

Verify or expand the search:

Other recruiting trials for Acute Lymphoblastic Leukemia

Currently open trials in the same condition.

Other Juno Therapeutics, a Subsidiary of Celgene trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02535364.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing