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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)

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
JCAR017
Lymphodepleting
Fludarabine
Cyclophosphamide
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Precursor Cell Lymphoblastic Leukemia-Lymphoma focused on measuring 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

Eligibility Criteria

undefined - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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:

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

Sites / Locations

  • Local Institution - 163Recruiting
  • Local Institution - 167
  • Local Institution - 166
  • Local Institution - 160Recruiting
  • Local Institution - 162Recruiting
  • Local Institution - 164
  • Local Institution - 165
  • Local Institution - 161Recruiting
  • Local Institution - 168
  • Local Institution - 601Recruiting
  • Local Institution - 602Recruiting
  • Local Institution - 600Recruiting
  • Local Institution - 501Recruiting
  • Local Institution - 500Recruiting
  • Local Institution - 301Recruiting
  • Local Institution - 300Recruiting
  • Local Institution - 400Recruiting
  • Local Institution - 251Recruiting
  • Local Institution - 250Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Administration of JCAR017

Arm Description

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

Outcomes

Primary Outcome Measures

Recommended Phase 2 Dose (RP2D) of JCAR017
The dose recommended for use in phase 2 studies on the basis of dose limiting toxicities observed in phase 1 studies.
Overall response rate (ORR)- Cohort 1
Total number of subjects achieving a Complete response (CR) or CR with incomplete blood count recovery (CRi) on Day 28 and confirmed on Day 56 as determined by IRC assessment.
Minimal residual disease (MRD) negative rate - Cohort 2
Total number of subjects achieving a CR or CRi with an MRD negative bone marrow (<0.01% tumor cells) on Day 28 and confirmed on Day 56 as determined by IRC assessment.
Overall response rate (ORR)- Cohort 3
Total number of subjects achieving a CR or PR on Day 28 as determined by IRC assessment.

Secondary Outcome Measures

Adverse Events (AEs)
Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups)
Overall response rate (ORR) in the non-selected dose levels from Phase 1
Percentage of r/r B-ALL subjects achieving a best overall response (BOR) of CR or CRi on Day 28, confirmed on Day 56 as determined by IRC assessment
Duration of response (DOR)
Time from first response until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first
Relapse-free survival (RFS)
Time from JCAR017 infusion to documentation of PD, disease relapse, or death due to any cause, whichever occurs first
Event-free survival (EFS)
Time from JCAR017 infusion to PD, disease relapse, start of a new anticancer therapy, or death from any cause, whichever occurs first
Overall survival (OS)
Time from JCAR017 infusion to time of death due to any cause
MRD negative response rate
Number of B-ALL subjects achieving CR or CRi and a negative MRD bone marrow.
Rate of hematopoietic stem cell transplant (HSCT) after response to JCAR017 infusion
Percentage of subjects who achieve a response after JCAR017 infusion and then proceed to HSCT
Pharmacokinetics - Cmax
Maximum concentration
Pharmacokinetics - Tmax
Time to peak concentration
Pharmacokinetics - AUC
Area under the curve
Best Overall Response (BOR)
Number of r/r B-NHL subjects achieving BOR of CR/PR

Full Information

First Posted
October 18, 2018
Last Updated
February 8, 2023
Sponsor
Celgene
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1. Study Identification

Unique Protocol Identification Number
NCT03743246
Brief Title
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)
Official Title
A Phase 1/2, Open-label, Single Arm, Multicohort, Multicenter Trial 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).
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 17, 2018 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
121 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Administration of JCAR017
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
JCAR017
Intervention Description
JCAR017
Intervention Type
Drug
Intervention Name(s)
Lymphodepleting
Intervention Description
Lymphodepleting
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide
Primary Outcome Measure Information:
Title
Recommended Phase 2 Dose (RP2D) of JCAR017
Description
The dose recommended for use in phase 2 studies on the basis of dose limiting toxicities observed in phase 1 studies.
Time Frame
28 days after JCAR017 infusion
Title
Overall response rate (ORR)- Cohort 1
Description
Total number of subjects achieving a Complete response (CR) or CR with incomplete blood count recovery (CRi) on Day 28 and confirmed on Day 56 as determined by IRC assessment.
Time Frame
Up to day 56
Title
Minimal residual disease (MRD) negative rate - Cohort 2
Description
Total number of subjects achieving a CR or CRi with an MRD negative bone marrow (<0.01% tumor cells) on Day 28 and confirmed on Day 56 as determined by IRC assessment.
Time Frame
Up to day 56
Title
Overall response rate (ORR)- Cohort 3
Description
Total number of subjects achieving a CR or PR on Day 28 as determined by IRC assessment.
Time Frame
On day 28
Secondary Outcome Measure Information:
Title
Adverse Events (AEs)
Description
Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups)
Time Frame
Up to 2 years after JCAR017 infusion
Title
Overall response rate (ORR) in the non-selected dose levels from Phase 1
Description
Percentage of r/r B-ALL subjects achieving a best overall response (BOR) of CR or CRi on Day 28, confirmed on Day 56 as determined by IRC assessment
Time Frame
On day 28 and day 56
Title
Duration of response (DOR)
Description
Time from first response until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first
Time Frame
Up to 2 years after JCAR017 infusion
Title
Relapse-free survival (RFS)
Description
Time from JCAR017 infusion to documentation of PD, disease relapse, or death due to any cause, whichever occurs first
Time Frame
Up to 2 years after JCAR017 infusion
Title
Event-free survival (EFS)
Description
Time from JCAR017 infusion to PD, disease relapse, start of a new anticancer therapy, or death from any cause, whichever occurs first
Time Frame
Up to 2 years after JCAR017 infusion
Title
Overall survival (OS)
Description
Time from JCAR017 infusion to time of death due to any cause
Time Frame
Up to 2 years after JCAR017 infusion
Title
MRD negative response rate
Description
Number of B-ALL subjects achieving CR or CRi and a negative MRD bone marrow.
Time Frame
Up to 2 years after JCAR017 infusion
Title
Rate of hematopoietic stem cell transplant (HSCT) after response to JCAR017 infusion
Description
Percentage of subjects who achieve a response after JCAR017 infusion and then proceed to HSCT
Time Frame
Up to 2 years after JCAR017 infusion
Title
Pharmacokinetics - Cmax
Description
Maximum concentration
Time Frame
Up to 2 years after JCAR017 infusion
Title
Pharmacokinetics - Tmax
Description
Time to peak concentration
Time Frame
Up to 2 years after JCAR017 infusion
Title
Pharmacokinetics - AUC
Description
Area under the curve
Time Frame
Up to 2 years after JCAR017 infusion
Title
Best Overall Response (BOR)
Description
Number of r/r B-NHL subjects achieving BOR of CR/PR
Time Frame
Up to 2 years after JCAR017 infusion

10. Eligibility

Sex
All
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: 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. Subject (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. Investigator considers the subject is appropriate for adoptive T cell therapy. Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or immunohistochemistry (bone marrow biopsy) Subject has a Karnofsky score of ≥ 50 (subjects ≥ 16 years of age) or a Lansky score ≥ 50 (subjects < 16 years of age). 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. 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. 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. Adequate vascular access for leukapheresis procedure. Participants must agree to use effective contraception Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment: Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 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. Subject has any condition that confounds the ability to interpret data from the study. Subject with a history of another primary malignancy that has not been in remission for at least 2 years prior to enrollment. Subjects who have received previous CD19-targeted therapy must have CD19-positive disease confirmed since completing the prior CD19-targeted therapy. Prior CAR T cell or other genetically-modified T cell therapy. Subject with a previous history of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection. 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. Subject has presence of acute or chronic graft-versus-host disease (GVHD). Subject with active autoimmune disease requiring immunosuppressive therapy. Subject has cardiac disorders (CTCAE version 4.03 Grade 3 or 4) within the past 6 months. Subject with a concomitant genetic syndrome, with the exception of Down's syndrome. 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. 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. Subject is pregnant or nursing. 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. Tumor invasion of venous or arterial vessels (B-NHL subjects only). 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. Existence of CD19-negative clone(s) of leukemia cells
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
BMS Study Connect Contact Center www.BMSStudyConnect.com
Phone
855-907-3286
Email
Clinical.Trials@bms.com
First Name & Middle Initial & Last Name or Official Title & Degree
First line of the email MUST contain NCT # and Site #.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution - 163
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 163
Facility Name
Local Institution - 167
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 167
Facility Name
Local Institution - 166
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 166
Facility Name
Local Institution - 160
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 160
Facility Name
Local Institution - 162
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 162
Facility Name
Local Institution - 164
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-7208
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 164
Facility Name
Local Institution - 165
City
Houston
State/Province
Texas
ZIP/Postal Code
70030
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 165
Facility Name
Local Institution - 161
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 161
Facility Name
Local Institution - 168
City
Wauwatosa
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 168
Facility Name
Local Institution - 601
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 601
Facility Name
Local Institution - 602
City
Marseille Cedex 01
ZIP/Postal Code
13005
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 602
Facility Name
Local Institution - 600
City
Paris
ZIP/Postal Code
75935
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 600
Facility Name
Local Institution - 501
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 501
Facility Name
Local Institution - 500
City
Frankfurt
ZIP/Postal Code
D-60590
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 500
Facility Name
Local Institution - 301
City
Monza
ZIP/Postal Code
20900
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 301
Facility Name
Local Institution - 300
City
Roma
ZIP/Postal Code
00165
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 300
Facility Name
Local Institution - 400
City
Utrecht
ZIP/Postal Code
3584 CS
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 400
Facility Name
Local Institution - 251
City
Esplugues de Llobregat
ZIP/Postal Code
08950
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 251
Facility Name
Local Institution - 250
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site 250

12. IPD Sharing Statement

Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

Learn more about this trial

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)

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