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TerminatedNCT03743246Updated Aug 15, 2024Results posted

A Study to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With Relapsed/Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL)

A Phase 1/2 interventional study of JCAR017 and Lymphodepleting in Precursor Cell Lymphoblastic Leukemia-Lymphoma and Lymphoma, Non-Hodgkin, sponsored by Celgene. Terminated at 19 sites in 6 countries. Open to participants aged Up to 25 Years. Per ClinicalTrials.gov, last updated 2024-08-15.

Sponsored by Celgene · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Absence of significant therapeutic benefit over existing therapies
Phase
Phase 1/2
Study type
Interventional
Enrollment
21
Allocation
Not applicable
Ages
Up to 25 Years
Sex
All
01

Study summary

This is a Phase 1/2, open-label, single arm, multicohort study to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged ≤ 25 years with CD19+ r/r B-ALL and B-NHL.

Phase 1 will identify a recommended Phase 2 dose (RP2D). Phase 2 will evaluate the efficacy of JCAR017 RP2D in the following three disease cohorts: Cohort 1 (r/r B-ALL), Cohort 2 (MRD+ B-ALL) and Cohort 3 (r/r B-NHL, [DLBCL, BL, or PMBCL]). A Simon's Optimal two-stage study design will be applied to Cohort 1 and 2 in Phase 2.

Read the detailed description

This is a Phase 1/2, open-label, single arm, multicohort study incorporating Simon's Optimal two-stage design to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged ≤ 25 years with CD19+ r/r B-ALL and B-NHL.

In the Phase 1, up to 5 dose levels will be of JCAR017 will be evaluated. Enrollment will commence in pediatric subjects with r/r B-ALL at Dose Level 1 (DL1) of 0.05x10\^6 CAR+ T cells/kg (maximum DL1 of 5x10\^6 JCAR017 CAR+ T cells [non-weight adjusted]). If this dose is confirmed to be safe and tolerable, additional subjects will be enrolled at higher dose(s) up to 0.75 x10\^6 CAR+ T cells/kg (maximum of 75x10\^6 JCAR017 CAR+ T cells [non-weight adjusted]) with the aim to identify the RP2D. Dose escalation/de-escalation will follow a modified toxicity probability interval (mTPI-2) algorithm. A Safety Review Committee (SRC) will recommend the Phase 2 dose (defined as RP2D) based on an integrated assessment of the safety, PK and preliminary efficacy information from at least 10 pediatric subjects treated at the RP2D.

In Phase 2, a minimum of 71 additional subjects (\< 18 years of age) will be enrolled into one of the 3 cohorts listed below. The sample size for Cohorts 1 and 2 is calculated according to Simon's Optimal two-stage design. The 10 or more pediatric subjects treated at the RP2D in Phase 1 will form part of the sample size (ie, Cohort 1 and Cohort 2). Therefore, the protocol intends to treat 81 primary endpoint evaluable pediatric subjects in Phase 2, if warranted by the evaluation of results at the completion of the first stage of the study in each cohort.

  • Cohort 1 (r/r B-ALL): 48 evaluable pediatric subjects (13 subjects in Stage 1 and 35 in Stage 2)
  • Cohort 2 (MRD+ B-ALL): 23 evaluable pediatric subjects (9 subjects in Stage 1 and 14 subjects in Stage 2)
  • Cohort 3 (r/r B-NHL [DLBCL, BL, or PMBCL]): 10 evaluable pediatric subjects. Due to the very low incidence rate and therefore expected low subject accrual, there is no formal sample size for this arm.

Up to 20 additional B-ALL subjects between 18 and 25 years of age may be enrolled in Phase 2.

Following treatment with JCAR017 subjects will then enter the post-treatment period for disease progression/relapse, safety, CAR T cell persistence, and survival up to 24 months after administration of JCAR017.

Efficacy will be assessed both locally and by an Independent Review Committee. Response assessments will be based on bone marrow and blood morphologic criteria, physical examination findings, along with laboratory assessments of cerebral spinal fluid (CSF) and bone marrow MRD (B-ALL only) assessments. B-NHL subjects will also have radiographic disease assessment by CT/MRI scans and tumor biopsies, if accessible.

Post-study follow-up for survival, relapse, long-term toxicity, and lentiviral vector safety will continue under a separate long-term follow-up protocol for up to 15 years after the JCAR017 infusion as per health authority regulatory guidelines.

An Independent Data Monitoring Committee will monitor the study conduct.

02

Conditions studied

  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, Non-Hodgkin

Keywords

  • Pediatric
  • JCAR017
  • CAR-T
  • CART
  • CD19
  • ALL
  • NHL
  • DLBCL
  • BL
  • PMBCL
  • Cell Therapy
  • LisoCell
  • Young Adults
  • Lymphoproliferative disorders
  • Immune system diseases
  • Leukemia
  • Lymphoma
  • lymphatic diseases
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 21 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

Celgene is the lead sponsor of 419 studies on the registry; 13 are open to participants now.

Of its 100 completed or terminated interventional studies of FDA-regulated products, 29 (29%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 25 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Subjects must satisfy the following criteria to be enrolled in the study:

  1. Phase 1: Subject \< 18 years of age and weighs ≥ 6 kg at the time of signing the informed consent form (ICF)/informed assent form (IAF).

    Phase 2: Subject ≤ 25 years of age and weighs ≥ 6 kg at the time of signing the ICF/IAF.

  2. Subject (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures.
  3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
  4. Investigator considers the subject is appropriate for adoptive T cell therapy.
  5. Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or immunohistochemistry (bone marrow biopsy)
  6. Subject has a Karnofsky score of ≥ 50 (subjects ≥ 16 years of age) or a Lansky score ≥ 50 (subjects \< 16 years of age).

  7. Diagnosis of B-cell ALL or B-cell NHL as defined below:

    Phase 1: Subjects with r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either of the following:

    • First or greater marrow relapse, or
    • Any marrow relapse after allogeneic HSCT, or
    • Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or
    • Ineligible for allogeneic HSCT Note: Subjects will be included regardless of MRD status.

    Phase 2: Subjects with one of the following:

    • Cohort 1: r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either:

      • First or greater marrow relapse, or
      • Any marrow relapse after allogeneic HSCT, or
      • Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or
      • Ineligible for allogeneic HSCT.

    • Cohort 2: MRD+ B-ALL, defined as:

      • \< 5% lymphoblasts by morphology with,
      • MRD detected by a validated assay at a frequency of 1 x10-4 or greater in BM cells. Subjects eligible for enrollment in Cohort 2 are those with MRD positive morphologic CR2 after re-induction when these subjects had previously experienced an early relapse (\< 36 months) after first-line chemotherapy. Subjects who are in MRD+ morphologic CR3 and later, regardless of time to relapse in earlier lines, are also eligible. Subjects who are in morphologic relapse at screening (r/r B-ALL) and become MRD+ after bridging chemotherapy are also eligible for treatment in Cohort 2.
    • Cohort 3: r/r B-NHL (DLBCL, BL or PMBCL), defined as measurable disease after 1 or more lines of chemotherapy and/or having failed HSCT or being ineligible for HSCT.

    Note: B-NHL subjects with secondary CNS lymphoma involvement are eligible however subject selection must consider clinical risk factors for severe neurological AEs and alternative treatment options. Subjects should only be enrolled if the Investigator considers the potential benefit outweighs the risk for the subject.

  8. Subjects with Philadelphia chromosome positive ALL are eligible if they are intolerant to or have failed one or more lines of tyrosine-kinase inhibitor (TKI) therapy or if TKI therapy is contraindicated.

  9. Adequate organ function, defined as:

    • Adequate BM function to receive LD chemotherapy as assessed by the Investigator.
    • Subject with adequate renal function, which is defined as:

    Serum creatinine based on age/gender as described below. Subjects that do not meet the criteria but who have a creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70 mL/min/1.73 m2 are eligible.• Alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN) and total bilirubin \< 2.0 mg/dL (or \< 3.0 mg/dL for subjects with Gilbert's syndrome or leukemic/lymphomatous infiltration of the liver).

    • Adequate pulmonary function, defined as ≤ Grade 1 dyspnea according to Common Toxicity Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) ≥ 92% on room air.
    • Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 4 weeks prior to leukapheresis.
  10. Adequate vascular access for leukapheresis procedure.
  11. Participants must agree to use effective contraception

Exclusion criteria

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

  1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  3. Subject has any condition that confounds the ability to interpret data from the study.
  4. Subject with a history of another primary malignancy that has not been in remission for at least 2 years prior to enrollment.
  5. Subjects who have received previous CD19-targeted therapy must have CD19-positive disease confirmed since completing the prior CD19-targeted therapy.
  6. Prior CAR T cell or other genetically-modified T cell therapy.
  7. Subject with a previous history of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
  8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion.
  9. Subject has presence of acute or chronic graft-versus-host disease (GVHD).
  10. Subject with active autoimmune disease requiring immunosuppressive therapy.
  11. Subject has cardiac disorders (CTCAE version 4.03 Grade 3 or 4) within the past 6 months.
  12. Subject with a concomitant genetic syndrome, with the exception of Down's syndrome.
  13. Subject with active CNS disease and significant neurological deterioration. Subjects with CNS-2 or CNS-3 involvement are eligible provided they are asymptomatic and do not have significant neurological deterioration and, in the opinion of the study investigator, the CNS disease burden can be controlled until JCAR017 infusion.
  14. Subject with a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
  15. Subject is pregnant or nursing.

  16. Subject has used the following:

    • Therapeutic doses of corticosteroids (defined as > 0.4 mg/kg maximum 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017 infusion. Physiologic replacement, topical, and inhaled steroids are permitted.
    • Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300 mg/m2) given after leukapheresis to maintain disease control must be stopped ≥ 7 days prior to LD chemotherapy.
    • Cytotoxic chemotherapeutic agents that are not considered lymphotoxic within 1 week prior to leukapheresis. Oral anticancer agents are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
    • Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) within 2 weeks prior to leukapheresis.
    • Experimental agents within 4 weeks prior to leukapheresis unless no response or PD is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis.
    • Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 infusion (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as antitumor necrosis factor [TNF], anti-IL-6, or anti-IL-6R).
    • Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 infusion.
    • Radiation within 6 weeks prior to leukapheresis. Subjects must have PD in irradiated lesions or have additional non-irradiated lesions to be eligible. Radiation to a single lesion, if additional non-irradiated, measurable lesions are present, is allowed up to 2 weeks prior to leukapheresis.
    • Allogeneic HSCT within 90 days prior to leukapheresis.
  17. Tumor invasion of venous or arterial vessels (B-NHL subjects only).
  18. Deep Venous Thrombosis (DVT) or Pulmonary Embolism (PE) within 3 months prior to leukapheresis. Subjects with DVT or PE that occurred longer than 3 months prior to leukapheresis, who still require ongoing therapeutic levels of anti-coagulation therapy, are also excluded.
  19. Existence of CD19-negative clone(s) of leukemia cells
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    Administration of JCAR017

    Subjects will receive Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) (flu/cy) concurrently, followed by JCAR017 cells infusion. Phase 1 will evaluate up to 5 JCAR017 cells dose levels and dose escalation/de-escalation will follow a modified toxicity probability interval (mTPI-2) algorithm. The declared RP2D in Phase 1 will be applied to the subjects enrolled in Phase 2

    Drug: JCAR017 · Drug: Lymphodepleting · Drug: Fludarabine · Drug: Cyclophosphamide

Interventions

  • DrugJCAR017

    JCAR017

  • DrugLymphodepleting

    Lymphodepleting

  • DrugFludarabine

    Fludarabine

  • DrugCyclophosphamide

    Cyclophosphamide

06

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion

    An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 30 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.

    Time frame: From first JCAR017 infusion (Day 1) to 30 days after JCAR017 infusion

  2. Number of Participants With Dose Limiting Toxicities

    A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to Grade ≤ 3 within 3 days * Gr 3 CRS that does not resolve to Grade ≤ 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \> 3 × ULN and concurrent increase in total bilirubin \> 2 × ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic Gr 3 or 4 event not pre-existing or not due to the underlying malignancy * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee

    Time frame: From first JCAR017 infusion (Day 1) to 28 days after JCAR017 infusion

  3. Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion

    Concentration of JCAR017 in Peripheral Blood was assessed by droplet digital polymerase chain reaction.

    Time frame: At day 28 post JCAR017 infusion

Secondary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion

    An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater. The following scale for grading was used - Grade 3 = Severe, Grade 4 = Life-Threatening.

    Time frame: From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion

  2. Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion

    Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/ birth defect; constitutes an important medical event. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.

    Time frame: From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion

  3. Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets

    Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

    Time frame: Baseline and at Day 28

  4. Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes

    Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

    Time frame: Baseline and at Day 28

  5. Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes

    Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

    Time frame: Baseline and at Day 28

  6. Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit

    Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

    Time frame: Baseline and at Day 28

  7. Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin

    Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

    Time frame: Baseline and at Day 28

  8. Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase

    Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

    Time frame: Baseline and at Day 28

  9. Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein

    Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

    Time frame: Baseline and at Day 28

  10. Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride

    Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

    Time frame: Baseline and at Day 28

  11. Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate

    Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

    Time frame: Baseline and at Day 28

  12. Number of Participants With Manufacturing Success of JCAR017 Product

    Successful product was defined as JCAR017 product was generated and able to be QC released (including nonconforming product) for infusion. Unsuccessful product is defined as no JCAR017 product could be generated after two manufacturing attempts using a single apheresis product for starting material or product was unable to be QC released for infusion.

    Time frame: From screening to JCAR017 infusion (day -35 to day 1)

  13. Overall Response Rate (ORR)

    ORR is defined as the percentage of participants who achieved either a complete response (CR) or complete response with incomplete blood recovery (CRi) on Day 28 that is confirmed on Day 56. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric acute lymphoblastic leukemia (ALL). CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL.

    Time frame: Up to Day 56

  14. Duration of Response (DOR)

    DOR is defined as time from first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric ALL. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.

    Time frame: From first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first (Up to approximately 14 months)

  15. Relapse Free Survival (RFS)

    RFS is defined as time from conforming JCAR017 infusion to the first progressive disease (PD), relapsed disease or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks.

    Time frame: Up to approximately 15 months

  16. Event Free Survival (EFS)

    EFS is defined as time from conforming JCAR017 infusion to progressive disease (PD), relapsed disease, start of a new anticancer therapy including HSCT or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. Only responders are included in he analysis. Censored participants were also analyzed.

    Time frame: From conforming JCAR017 infusion to PD, relapsed disease, start of a new anticancer therapy including Hematopoietic Stem Cell Transplant (HSCT) or death from any cause, whichever occurs first (Up to approximately 15 months)

  17. Overall Survival (OS)

    OS is defined as the interval from the date of first confirming JCAR017 infusion to the date of death due to any reason.

    Time frame: From the date of first confirming JCAR017 infusion to the date of death due to any reason (Up to approximately 24 months)

  18. Minimal Residual Response (MRD) Negative Response Rate

    Minimal Residual Disease (MRD) Negative Response Rate is defined as the percentage of participants achieving either a CR or CRi with a MRD negative bone marrow on Day 28, confirmed on Day 56. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Disease assessments recorded on or after start of a new anticancer therapy, including HSCT, will not be considered, nor will disease assessments reported after a PD or relapse has been observed.

    Time frame: Up to Day 56

  19. Number of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant

    Number of participants who undergo HSCT after receiving a JCAR017 infusion and achieving a response are presented. The time of proceeding to HSCT is defined as the time of commencing the conditioning regimen as required for HSCT. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.

    Time frame: Up to approximately 24 months

07

Results

Posted Aug 15, 2024
Limitations and caveats
The study was terminated and hence participants were not enrolled in Phase 2 cohorts (r/r B-ALL; MRD+ B-ALL; r/r B-NHL).

Participant flow

Pre-Treatment Period
Participant flow — Pre-Treatment Period
Milestone0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot Assigned
Started9831
Completed8710
Not completed1121
Withdrew: Failure to meet treatment criteria0020
Withdrew: Death0101
Withdrew: Study drug manufacturing failure1000
Lymphodepleting Chemotherapy
Participant flow — Lymphodepleting Chemotherapy
Milestone0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot Assigned
Started8710
Completed7710
Not completed1000
Withdrew: Progressive disease1000
Treatment Period (JCAR017 Infusion)
Participant flow — Treatment Period (JCAR017 Infusion)
Milestone0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot Assigned
Started7710
Completed3610
Not completed4100
Withdrew: Other reason1000
Withdrew: Lost to follow-up0100
Withdrew: Progressive disease1000
Withdrew: Death1000
Withdrew: Study terminated by sponsor1000

Outcome measures

PrimaryNumber of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion

An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 30 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.

Time frame:
From first JCAR017 infusion (Day 1) to 30 days after JCAR017 infusion
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion
Participants0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion761
PrimaryNumber of Participants With Dose Limiting Toxicities

A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to Grade ≤ 3 within 3 days * Gr 3 CRS that does not resolve to Grade ≤ 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \> 3 × ULN and concurrent increase in total bilirubin \> 2 × ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic Gr 3 or 4 event not pre-existing or not due to the underlying malignancy * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee

Time frame:
From first JCAR017 infusion (Day 1) to 28 days after JCAR017 infusion
Reported as:
Count of participants · Participants
Number of Participants With Dose Limiting Toxicities
Participants0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Number of Participants With Dose Limiting Toxicities021
PrimaryConcentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion

Concentration of JCAR017 in Peripheral Blood was assessed by droplet digital polymerase chain reaction.

Time frame:
At day 28 post JCAR017 infusion
Reported as:
Geometric mean · copies per microgram
Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion
copies per microgram0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion1131.821 ± 64.6581457.591 ± 75.5582847.910 ± NA
SecondaryNumber of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion

An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater. The following scale for grading was used - Grade 3 = Severe, Grade 4 = Life-Threatening.

Time frame:
From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion
Participants0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
At least one TEAE761
At least one grade 3/4 TEAE651
At Least One TEAE Related To JCAR017551
At Least One grade 3/4 TEAE Related To JCAR017341
SecondaryNumber of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion

Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/ birth defect; constitutes an important medical event. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.

Time frame:
From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion
Reported as:
Count of participants · Participants
Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion
Participants0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
AT Least one Serious TEAE531
At Least One Serious TEAE Related To JCAR017131
SecondaryChange From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Time frame:
Baseline and at Day 28
Reported as:
Mean · 10^9 cells/L
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets
10^9 cells/L0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Basophils0.00 ± 0.025-0.01 ± 0.023-0.01 ± NA
Eosinophils0.03 ± 0.0480.08 ± 0.114-0.08 ± NA
Leukocytes4.01 ± 8.3380.59 ± 1.753-2.00 ± NA
Lymphocytes-0.22 ± 0.8790.27 ± 1.286-0.57 ± NA
Monocytes0.11 ± 0.1630.09 ± 0.173-0.22 ± NA
Neutrophils0.41 ± 0.782-0.18 ± 0.735-1.50 ± NA
Platelets27.33 ± 132.672-68.60 ± 168.583-163.00 ± NA
SecondaryChange From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Time frame:
Baseline and at Day 28
Reported as:
Mean · Ratio
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes
Ratio0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Basophils/Leukocytes0.25 ± 0.885-0.24 ± 0.654-0.30 ± NA
Eosinophils/Leukocytes0.85 ± 1.4024.28 ± 5.389-2.90 ± NA
Lymphocytes/Leukocytes-29.57 ± 21.690-16.30 ± 25.14033.80 ± NA
Neutrophils/Leukocytes26.45 ± 26.81510.70 ± 18.797-33.90 ± NA
Monocytes/Leukocytes4.35 ± 10.1231.74 ± 4.5150.20 ± NA
SecondaryChange From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Time frame:
Baseline and at Day 28
Reported as:
Mean · 10^12 cells/L
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes
10^12 cells/L0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes0.04 ± 0.7810.08 ± 0.268-0.70 ± NA
SecondaryChange From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Time frame:
Baseline and at Day 28
Reported as:
Mean · proportion of red blood cells in blood
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit
proportion of red blood cells in blood0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit0.00 ± 0.0680.02 ± 0.016-0.03 ± NA
SecondaryChange From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Time frame:
Baseline and at Day 28
Reported as:
Mean · grams per liter
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin
grams per liter0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin2.33 ± 24.3126.20 ± 6.834-13.00 ± NA
SecondaryChange From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Time frame:
Baseline and at Day 28
Reported as:
Mean · units per liter
Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase
units per liter0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Alanine aminotransferase5.33 ± 19.4394.50 ± 16.299-19.00 ± NA
Alkaline phosphatase53.50 ± 158.32278.75 ± 40.950-121.00 ± NA
Aspartate aminotransferase29.17 ± 72.20411.50 ± 13.675-1.00 ± NA
Lactate dehydrogenase992.33 ± 2238.88822.25 ± 43.684-36.00 ± NA
SecondaryChange From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Time frame:
Baseline and at Day 28
Reported as:
Mean · grams per liter
Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein
grams per liter0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Albumin5.83 ± 9.6636.75 ± 2.062-3.00 ± NA
Protein4.00 ± 12.6025.00 ± 6.683-6.00 ± NA
SecondaryChange From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Time frame:
Baseline and at Day 28
Reported as:
Mean · mmol/L
Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride
mmol/L0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Bicarbonate2.53 ± 4.453-2.65 ± 1.9194.10 ± NA
Blood Urea Nitrogen3.60 ± 3.5422.43 ± 0.8260.20 ± NA
Calcium0.13 ± 0.1570.04 ± 0.058-0.17 ± NA
Chloride-1.50 ± 4.3241.50 ± 1.2911.00 ± NA
Glucose0.32 ± 0.641-0.08 ± 0.47214.90 ± NA
Magnesium0.06 ± 0.1070.06 ± 0.1090.00 ± NA
Phosphate0.02 ± 0.281-0.02 ± 0.336-0.16 ± NA
Potassium-0.05 ± 0.6720.20 ± 0.5351.50 ± NA
Sodium1.00 ± 2.6082.25 ± 2.2172.00 ± NA
Triglyceride0.45 ± 1.6520.29 ± 0.3200.33 ± NA
SecondaryChange From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Time frame:
Baseline and at Day 28
Reported as:
Mean · umol/L
Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate
umol/L0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Bilirubin20.26 ± 41.498-1.00 ± 6.9282.00 ± NA
Creatinine9.84 ± 14.2181.50 ± 9.000-2.00 ± NA
Direct Bilirubin13.44 ± 33.601-0.25 ± 0.5000.00 ± NA
Urate43.51 ± 94.08185.00 ± 71.6159.00 ± NA
SecondaryNumber of Participants With Manufacturing Success of JCAR017 Product

Successful product was defined as JCAR017 product was generated and able to be QC released (including nonconforming product) for infusion. Unsuccessful product is defined as no JCAR017 product could be generated after two manufacturing attempts using a single apheresis product for starting material or product was unable to be QC released for infusion.

Time frame:
From screening to JCAR017 infusion (day -35 to day 1)
Reported as:
Count of participants · Participants
Number of Participants With Manufacturing Success of JCAR017 Product
Participants0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot Assigned
Number of Participants With Manufacturing Success of JCAR017 Product7721
SecondaryOverall Response Rate (ORR)

ORR is defined as the percentage of participants who achieved either a complete response (CR) or complete response with incomplete blood recovery (CRi) on Day 28 that is confirmed on Day 56. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric acute lymphoblastic leukemia (ALL). CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL.

Time frame:
Up to Day 56
Reported as:
Number · percentage of participants
Overall Response Rate (ORR)
percentage of participants0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Overall Response Rate (ORR)50.0 (11.8 to 88.2)25.0 (0.6 to 80.6)100.0 (2.5 to 100.0)
SecondaryDuration of Response (DOR)

DOR is defined as time from first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric ALL. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.

Time frame:
From first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first (Up to approximately 14 months)
Reported as:
Median · months
Duration of Response (DOR)
months0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Duration of Response (DOR)13.70 (2.46 to 13.70)NA (4.93 to 4.93)NA (2.23 to 2.23)
SecondaryRelapse Free Survival (RFS)

RFS is defined as time from conforming JCAR017 infusion to the first progressive disease (PD), relapsed disease or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks.

Time frame:
Up to approximately 15 months
Reported as:
Median · months
Relapse Free Survival (RFS)
months0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Relapse Free Survival (RFS)7.77 (0.46 to 14.62)6.98 (1.15 to 8.97)NA (3.12 to 3.12)
SecondaryEvent Free Survival (EFS)

EFS is defined as time from conforming JCAR017 infusion to progressive disease (PD), relapsed disease, start of a new anticancer therapy including HSCT or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. Only responders are included in he analysis. Censored participants were also analyzed.

Time frame:
From conforming JCAR017 infusion to PD, relapsed disease, start of a new anticancer therapy including Hematopoietic Stem Cell Transplant (HSCT) or death from any cause, whichever occurs first (Up to approximately 15 months)
Reported as:
Median · months
Event Free Survival (EFS)
months0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Event Free Survival (EFS)3.24 (0.46 to 14.62)5.42 (1.15 to 8.97)3.12 (3.12 to 3.12)
SecondaryOverall Survival (OS)

OS is defined as the interval from the date of first confirming JCAR017 infusion to the date of death due to any reason.

Time frame:
From the date of first confirming JCAR017 infusion to the date of death due to any reason (Up to approximately 24 months)
Reported as:
Median · months
Overall Survival (OS)
months0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Overall Survival (OS)7.13 (0.76 to NA)7.08 (4.99 to NA)8.90 (NA to NA)
SecondaryMinimal Residual Response (MRD) Negative Response Rate

Minimal Residual Disease (MRD) Negative Response Rate is defined as the percentage of participants achieving either a CR or CRi with a MRD negative bone marrow on Day 28, confirmed on Day 56. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Disease assessments recorded on or after start of a new anticancer therapy, including HSCT, will not be considered, nor will disease assessments reported after a PD or relapse has been observed.

Time frame:
Up to Day 56
Reported as:
Number · percentage of participants
Minimal Residual Response (MRD) Negative Response Rate
percentage of participants0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Minimal Residual Response (MRD) Negative Response Rate16.7 (0.4 to 64.1)25.0 (0.6 to 80.6)100.0 (2.5 to 100.0)
SecondaryNumber of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant

Number of participants who undergo HSCT after receiving a JCAR017 infusion and achieving a response are presented. The time of proceeding to HSCT is defined as the time of commencing the conditioning regimen as required for HSCT. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.

Time frame:
Up to approximately 24 months
Reported as:
Count of participants · Participants
Number of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant
Participants0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kg
Number of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant111

Adverse events

Collected over All-cause mortality was collected from JCAR017 infusion until their study completion (up to approximately 1928 days). Serious and non-serious adverse events were collected from first JCAR017 infusion (Day 1) to 90 days post JCAR017 infusion.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
0.05 x 10^6 CAR+ T Cells/kg6/9 (66.7%)5/7 (71.4%)7/7 (100%)
0.15 x 10^6 CAR+ T Cells/kg4/8 (50%)3/6 (50%)6/6 (100%)
0.50 x 106 CAR+T Cells/kg1/3 (33.3%)1/1 (100%)1/1 (100%)
Not Assigned1/1 (100%)——
Most frequent serious events
Most frequent serious events
Event0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot Assigned
Brain oedemaNervous system disorders0/70/61/1—
NeurotoxicityNervous system disorders1/71/61/1—
Cytokine release syndromeImmune system disorders0/73/60/1—
Infusion related reactionInjury, poisoning and procedural complications0/71/60/1—
PneumoniaInfections and infestations1/70/60/1—
SepsisInfections and infestations1/70/60/1—
ViraemiaInfections and infestations1/70/60/1—
Extradural haematomaInjury, poisoning and procedural complications1/70/60/1—
Most frequent other events
Showing 10 of 78
Most frequent other events
Event0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot Assigned
AnaemiaBlood and lymphatic system disorders5/75/61/1—
CoagulopathyBlood and lymphatic system disorders0/70/61/1—
LeukopeniaBlood and lymphatic system disorders4/71/61/1—
NeutropeniaBlood and lymphatic system disorders3/72/61/1—
ThrombocytopeniaBlood and lymphatic system disorders4/73/61/1—
BradycardiaCardiac disorders0/71/61/1—
TachycardiaCardiac disorders0/70/61/1—
DiarrhoeaGastrointestinal disorders0/71/61/1—
Cytokine release syndromeImmune system disorders4/71/61/1—
HypogammaglobulinaemiaImmune system disorders1/71/61/1—

Baseline characteristics

Age, Customized
Age, Customized(participants)0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot AssignedTotal
< 6 years34209
>= 6 to < 12 years53109
>= 12 to < 18 years11013
Sex: Female, Male
Sex: Female, Male(Participants)0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot AssignedTotal
Female542011
Male441110
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot AssignedTotal
Hispanic or Latino43119
Not Hispanic or Latino442010
Unknown or Not Reported11002
Race (NIH/OMB)
Race (NIH/OMB)(Participants)0.05 x 10^6 CAR+ T Cells/kg0.15 x 10^6 CAR+ T Cells/kg0.50 x 106 CAR+T Cells/kgNot AssignedTotal
American Indian or Alaska Native11013
Asian00000
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White653014
More than one race00000
Unknown or Not Reported22004
08

Study locations

19 sites
  • Local Institution - 163
    Duarte, California 91010, United States
  • Local Institution - 167
    Redwood City, California 94063, United States
  • Local Institution - 166
    Saint Petersburg, Florida 33701, United States
  • Local Institution - 160
    New York, New York 10021, United States
  • Local Institution - 162
    Philadelphia, Pennsylvania 19104, United States
  • Local Institution - 164
    Dallas, Texas 75390-7208, United States
  • Local Institution - 165
    Houston, Texas 77030, United States
  • Local Institution - 161
    Seattle, Washington 98105, United States
  • Local Institution - 168
    Wauwatosa, Wisconsin 53226, United States
  • Local Institution - 601
    Lyon, 69008, France
  • Local Institution - 602
    Marseille Cedex 01, 13005, France
  • Local Institution - 600
    Paris, 75935, France
  • Local Institution - 501
    Berlin, 13353, Germany
  • Local Institution - 500
    Frankfurt, D-60590, Germany
  • Local Institution - 301
    Monza, 20900, Italy
  • Local Institution - 300
    Roma, 00165, Italy
  • Local Institution - 400
    Utrecht, 3584 CS, Netherlands
  • Local Institution - 251
    Esplugues de Llobregat, 08950, Spain
  • Local Institution - 250
    Madrid, 28009, Spain
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Sep 10, 2019

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 15, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03743246
Lead sponsor
Celgene
Responsible party
Sponsor
First posted
Nov 16, 2018
Start date
Oct 17, 2018
Primary completion
Jan 26, 2024
Completion
Jan 26, 2024
Results posted
Aug 15, 2024
Last update
Aug 15, 2024

Study contacts

Bristol-Myers Squibb
study director · Bristol-Myers Squibb

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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