A Phase 2, Open-label, Multiple Cohort, Single-arm, Multi-center Trial to Determine the Safety, Feasibility and Efficacy of JCAR015 in Adult Subjects With B-cell Acute Lymphoblastic Leukemia.

Celgene18 sites in 7 countriesDecember 20, 2016

ConditionsPrecursor Cell Lymphoblastic Leukemia-Lymphoma

InterventionsJCAR015

DrugsJCAR015

Overview

Phase: Phase 1
Intervention: JCAR015
Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Sponsor: Celgene
Locations: 18
Primary Endpoint: Overall Response Rate (ORR)
Status: Withdrawn
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-arm, multi-center, open-label, Phase 2 study to determine the efficacy and safety of JCAR015 in adult subjects with B-cell ALL. The study is divided into two sequential parts, Part A and Part B; subjects will be screened and will provide informed consent before initiating any study procedures in Part A of the study.

Registry

clinicaltrials.gov

Start Date

December 20, 2016

End Date

January 24, 2021

Last Updated

9 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Celgene

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥18 years at the time of signing the informed consent form
•Subject must understand and voluntarily sign an Informed consent form (ICF) prior to any study-related assessments/procedures being conducted
•Subject is willing and able to adhere to the study visit schedule and other protocol requirements
•Diagnosis of B-cell Acute Lymphoblastic Leukemia (ALL)
•Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or immunohistochemistry (bone marrow biopsy)
•Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
•No contraindications to cyclophosphamide. This includes subjects with:
•hypersensitivity to cyclophosphamide, any of its metabolites
•acute infections
•bone marrow aplasia or bone marrow depression prior to treatment

Exclusion Criteria

•Isolated extramedullary disease relapse
•Concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome
•Burkitt's lymphoma/leukemia or chronic myelogenous leukemia (CML) lymphoid blast crisis (p210 BCR-ABL+)
•Prior malignancy, unless treated with curative intent and with no evidence of active disease present for \> 5 years before signing the informed consent form, with the following exceptions:
•a. Subjects with Stage I breast cancer that has been completely and successfully treated, requiring no therapy or only anti-hormonal therapy b. Subjects with T1N0M0 or T2N0M0 colorectal cancer who have been completely and successfully resected and who are disease-free for \> 2 years prior to screening c. Subjects with indolent prostate cancer, defined as clinical stage T1 or T2a, Gleason score ≤ 6, and prostate-specific antigen (PSA) \< 10 ng/mL, requiring no therapy or only anti- hormonal therapy d. Subjects with a history of basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, fully resected, and with no evidence of active disease
•Treatment with any prior gene therapy product
•Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of signing the informed consent form
•Systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) at the time of signing the informed consent form
•Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of signing the informed consent form
•Active C S involvement by malignancy, defined as CNS-3 per NCCN guidelines. Subjects with a history of Central nervous system (CNS) disease that has been effectively treated (defined as one documented negative CSF evaluation within 1 month prior to signing the informed consent form) will be eligible

Arms & Interventions

JCAR015 administration

Single dose of 1.0-3.0 mg/m\^2 IV cyclophosphamide, JCAR015 Dose 1 1x10\^6 Tcells/kg, JCAR015 Dose 2 3x10\^6 Tcells/kg

Intervention: JCAR015

Outcomes

Primary Outcomes

Overall Response Rate (ORR)

Time Frame: Up to 6 months

The primary efficacy endpoint (for Cohorts 1-4) is ORR as determined by an Independent Review Committee (IRC). The ORR is, defined as proportion of subjects with a best overall response of Complete response (CR) or Complete response with incomplete peripheral blood count recovery (CRi) from 28 days through 6 months after the final infusion of JCAR015 or the start of receiving another anti-cancer therapy whichever comes first.

Minimal residual disease (MRD)

Time Frame: Up to 90 days

Evaluate the proportion of subjects who achieve a MRD negative complete response (CR) and the duration of MRD negative status, if achieved, after JCAR015 administration.