Neoplasms

Blood and Lymph Conditions

Immune System Diseases

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Lymphoma

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Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphoma, B-Cell

Lymphatic Diseases

Neoplasms by Histologic Type

Immunoproliferative Disorders

Hematologic Diseases

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Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

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

JCAR017

Lymphodepleting

Bristol-Myers Squibb

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.

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.

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, 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).

The dose recommended for use in phase 2 studies on the basis of dose limiting toxicities observed in phase 1 studies.

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.

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.

Total number of subjects achieving a CR or PR on Day 28 as determined by IRC assessment.

Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups)

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 from first response until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first

Time from JCAR017 infusion to documentation of PD, disease relapse, or death due to any cause, whichever occurs first

Time from JCAR017 infusion to PD, disease relapse, start of a new anticancer therapy, or death from any cause, whichever occurs first

Time from JCAR017 infusion to time of death due to any cause

Number of B-ALL subjects achieving CR or CRi and a negative MRD bone marrow.

Percentage of subjects who achieve a response after JCAR017 infusion and then proceed to HSCT

Number of r/r B-NHL subjects achieving BOR of CR/PR

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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)	NCT03743246	Precursor Cell ... Lymphoma, Non-H...	JCAR017 Lymphodepleting Fludarabine Cyclophosphamid...	- 25 Years	Celgene
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)	NCT03743246	Precursor Cell ... Lymphoma, Non-H...	JCAR017 Lymphodepleting Fludarabine Cyclophosphamid...	- 25 Years	Celgene
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)	NCT03743246	Precursor Cell ... Lymphoma, Non-H...	JCAR017 Lymphodepleting Fludarabine Cyclophosphamid...	- 25 Years	Celgene

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