A Study to Evaluate the Efficacy and Safety of JCAR017 in Adult Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma (NHL) (TRANSCEND FL)

A Phase 2, Open-label, Single Arm, Multicohort, Multicenter Trial to Evaluate the Efficacy and Safety of JCAR017 in Adult Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma (NHL)

This is a global Phase 2, open-label, single-arm, multicohort, multicenter study to evaluate efficacy and safety of JCAR017 in adult subjects with r/r FL or MZL.

The study will be conducted in compliance with the International Council on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.

This study is divided into three periods:

• Pretreatment, which consists of screening assessments, leukapheresis and the Pretreatment evaluation;
• Treatment, which starts with the administration of lymphodepleting (LD) chemotherapy and continues through JCAR017 administration at Day 1 with follow-up through Day 29;
• Posttreatment, which includes follow-up assessments for disease status and safety for 5 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: JCAR017

• Study Type: Interventional
• Enrollment (Estimated): 213
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Local Institution - UNK-201
  • Wien, Austria, 1090
    • Local Institution - 450
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 150
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Local Institution - 151
• France
  • Lille, France, 59037
    • Local Institution - 252
  • Montpellier CEDEX 5, France, 34295
    • Local Institution - 251
  • Pierre-Benite CEDEX, France, 69495
    • Local Institution - 250
• Germany
  • Köln, Germany, 50937
    • Local Institution - 501
  • Munich, Germany, 81377
    • Local Institution - 502
  • Ulm, Germany, 89081
    • Local Institution - 500
• Italy
  • Bergamo, Italy, 24127
    • Local Institution - 300
  • Naples, Italy, 80131
    • Local Institution - 301
• Japan
  • Fukuoka, Japan, 812-8582
    • Local Institution - 552
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 0608648
      • Local Institution - 553
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Local Institution - 550
    • Minato-ku, Tokyo, Japan, 105-8470
      • Local Institution - 551
• Spain
  • Salamanca, Spain, 37007
    • Local Institution - 350
  • Sevilla, Spain, 41013
    • Local Institution - 351
• Sweden
  • Stockholm, Sweden, 14186
    • Local Institution - 600
• United Kingdom
  • London, United Kingdom, NW1 2PG
    • Local Institution - 200
  • Manchester, United Kingdom, M20 4BX
    • Local Institution - 201
• United States
  • California
    • Santa Monica, California, United States, 90095
      • Local Institution - 111
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 107
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 105
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution - 103
    • Niles, Illinois, United States, 60714
      • Local Institution - 109
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Local Institution - 102
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 100
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 101
  • New York
    • New York, New York, United States, 10021
      • Local Institution - 116
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 110
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 112
  • Oregon
    • Portland, Oregon, United States, 97213
      • Local Institution - 114
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 117
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Local Institution - 113
  • Texas
    • Houston, Texas, United States, 77030
      • Local Institution - 104
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Local Institution - 115
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 108

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Relapsed or refractory follicular lymphoma (FL) (Grade 1, 2 or 3a) or marginal zone lymphoma (MZL) histologically confirmed within 6 months of screening, as assessed by local pathology
2. Patients should have received at least one prior therapy that includes anti-CD20 and alkylating agent
3. Follicular lymphoma patients: Received at least one prior line of systemic therapy. Patients that received one prior line of systemic therapy are eligible if they present with high risk features. Patients that received two or more prior lines of systemic therapy are eligible, assuming one of the prior lines includes anti-CD20 and alkylating agent (as listed in criterion 2)
4. Marginal zone lymphoma patients: Received two or more prior lines of systemic therapy, assuming one of the prior lines includes anti-CD20 and alkylating agent (as listed in criterion 2) or relapsed after hematopoietic stem cell transplant
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Adequate organ function
7. Adequate vascular access for leukapheresis procedure

Exclusion Criteria:

1. Evidence or history of composite Diffuse large B-cell lymphoma (DLBCL) and FL, or of transformed FL
2. WHO subclassification of duodenal-type FL
3. Central nervous system-only involvement by malignancy (subjects with secondary central nervous system (CNS) involvement are allowed on study)
4. History of another primary malignancy that has not been in remission for at least 2 years, with the exception of non-invasive malignancies
5. Prior CAR T-cell or other genetically-modified cell therapy
6. History of or active human immunodeficiency virus (HIV)
7. Active hepatitis B or active hepatitis C
8. Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment
9. Active autoimmune disease requiring immunosuppressive therapy
10. Presence of acute or chronic graft-versus-host=disease
11. History of significant cardiovascular disease
12. History or presence of clinically relevant central nervous system pathology
13. Allogenic-hematopoietic stem cell transplant (Allo-HSCT) within 90 days of leukapheresis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Administration of JCAR017; Subjects will be treated with fludarabine IV (30 mg/m2/day for 3 days) and cyclophosphamide IV (300 mg/m2/day for 3 days) prior to JCAR017 infusion. Refer to the most recent package inserts for further details on administration of these agents.; JCAR017 will be infused on Day 1 at a target dose of 100 × 10^6 CAR-positive viable T cells (CAR+ T cells), 2 to 7 days after completion of LD chemotherapy. Each JCAR017 dose includes CD4+ CAR+ T cells and CD8+ CAR+ T cells.

Drug: Fludarabine; Fludarabine; Drug: Cyclophosphamide; Cyclophosphamide; Drug: JCAR017; JCAR017

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Is defined as the percentage of participants achieving either a partial response (PR) or complete response (CR) at any time up to 60 months after JCAR017 treatment as assessed by PET-CT and/or CT using "The Lugano classification"	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CRR) as assessed but PET-CT and/or CT using "The Lugano Classification"	Is defined as the percentage of subjects achieving a CR at any time up to 60 months after JCAR017 treatment	Up to 60 months
Duration of Response (DOR) if Best Overall Response (BOR) is CR, as assessed by PET-CT and/or CT using "The Lugano Classification"	is defined for subjects with a BOR of CR as the time from first response (CR or PR) to disease progression or death from any cause up to 60 months after JCAR017 treatment	Up to 60 months
Duration of Response (DOR) as assessed by PET-CT and/or CT using "The Lugano Classification"	is defined as the time from first response (CR or PR) to disease progression or death from any cause, whichever occurs first up to 60 months after JCAR017 treatment	Up to 60 months
Progression-Free Survival (PFS) as assessed by PET-CT and/or CT using "The Lugano Classification"	is defined as the time from start of JCAR017 to disease progression or death from any cause, whichever occurs first up to 60 months after JCAR017 treatment	Up to 60 months
Overall Survival (OS)	is defined as the time from start of JCAR017 to time of death due to any cause up to 60 months after JCAR017 treatment	Up to 60 months
Adverse Events (AEs)	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.	Up to 60 months
Pharmacokinetics - Cmax	Maximum concentration	Up to 60 months
Pharmacokinetics - Tmax	Time to maximum concentration	Up to 60 months
Pharmacokinetics - AUC	Area under the curve	Up to 60 months
European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30)	is questionnaire that will be used as a measure of health-related quality of life. The EORTC QLQ-C30 is composed of both multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/health-related quality of life (HRQoL) scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale.	Up to 24 months
Functionality Assessment of Cancer Therapy Lymphoma Subscale (FACT-LymS)	is a 15-item lymphoma-specific additional concerns subscale. This subscale addresses symptoms and functional limitations are important to lymphoma patients. The FACT-LymS items are scored on a 0 ("Not at all") to 4 ("Very much") response scale. Items are aggregated to a single score on a 0-60 scale. High scores indicate lower symptom burden.	Up to 24 months

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2020
• Primary Completion (Estimated): September 28, 2028
• Study Completion (Estimated): September 28, 2028

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Follicular Lymphoma; Marginal Zone Lymphoma; Relapsed or Refractory; JCAR017; B-cell Non-Hodgkin Lymphoma (NHL)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: JCAR017-FOL-001; U1111-1244-9768 (Other Identifier: WHO); 2019-004081-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No