A Study to Determine Safety, Feasibility and Efficacy of JCAR015 in Adult Subjects With B-Cell Acute Lymphoblastic Leukemia

NCT02973191 | Withdrawn Phase 1 DMC

• 1 other identifier: JCAR015-ALL-001
• Study Type: interventional
• Target: N/A
• Locations: 7 countries
• Sites: 18

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.

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Keywords

Leukemia; B-Cell Acute Lymphoblastic Leukemia; JCAR015

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  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.

  Up to 6 months

• Minimal residual disease (MRD)

  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.

  Up to 90 days

Secondary Outcomes (11)

• Adverse Events (AEs)

  Up to 2 years

• Duration of Minimal residual disease (MRD) response

  Up to 24 months

• Relapse-free survival (RFS)

  Up to 24 months

• Event-free survival (EFS)

  Up to 24 months

• Overall survival (OS)

  Up to 24 months

Study Arms (1)

JCAR015 administration

EXPERIMENTAL

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

Drug: JCAR015

Interventions

JCAR015 DRUG

JCAR015 administration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• urinary tract infection
• acute urothelial toxicity from cytotoxic chemotherapy or radiation therapy
• urinary outflow obstruction
• obstruction
• Adequate organ function, defined as:

You may not qualify if:

• 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
• History of any one of the following cardiovascular conditions within the past 6 months of signing the informed consent form: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
• History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
• Participation in an investigational research study using an investigational agent within 30 days of signing the informed consent form, with the exception of investigational antiinfective agents (eg, antibacterial, antifungal, antiviral)
• Pregnant or nursing (lactating) women
• Use of prohibited medications:

Sponsors & Collaborators

• Celgene: lead
• Juno: collaborator

Study Sites (18)

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

University de Lille

Lille, 59037, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

University of Cologne

Cologne, 50924, Germany

Location

Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden

Dresden, 1307, Germany

Location

Universitatsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

University of Munich Grosshadern

Grosshadern Campus, D-81377, Germany

Location

University of Leipzig

Leipzig, 4103, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Istituto Clinico Humanitas - Istituti di Ricovero E Cura A Carattere Scientifico (IRCSS)

Milan, 20089, Italy

Location

Universita La Sapienza

Roma, 00168, Italy

Location

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

ICO-Hospital Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Chuv Bh-04

Lausanne, 1011, Switzerland

Location

Bristol Royal Infirmary, University of Bristol Foundation Trust

Bristol, BS2 8BJ, United Kingdom

Location

UCL Cancer Institute

London, WC1E 6BT, United Kingdom

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Burkitt Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Study Officials

• Jens Hasskarl, MD

  Celgene Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: November 25, 2016
• Study Start: December 20, 2016
• Primary Completion: June 25, 2019
• Study Completion: January 24, 2021
• Last Updated: April 10, 2017

Record last verified: 2017-04

Locations

GB (2); ES (2); DE (6); BE (1); CH (1); FR (2); IT (4)