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

Phase 2

Recruiting

• Conditions: Lymphoma, Non-Hodgkin
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: JCAR017

• Registration Number: NCT04245839
• Lead Sponsor: Celgene

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-27
• Study First Submitted QC: 2020-01-27
• Study First Posted: 2020-01-29
• Study Start: 2020-07-14
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-22
• Last Update Posted: 2025-05-23
• Primary Completion: 2031-09-30
• Study Completion: 2031-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 276

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Administration of JCAR017	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.
Administration of JCAR017	Fludarabine	* 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.
Administration of JCAR017	Cyclophosphamide	* 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.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to 60 months	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"

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR) if Best Overall Response (BOR) is CR, as assessed by PET-CT and/or CT using "The Lugano Classification"	Up to 60 months	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
Pharmacokinetics - Tmax	Up to 60 months	Time to maximum concentration
Pharmacokinetics - AUC	Up to 60 months	Area under the curve
Functionality Assessment of Cancer Therapy Lymphoma Subscale (FACT-LymS)	Up to 24 months	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.
Complete response rate (CRR) as assessed but PET-CT and/or CT using "The Lugano Classification"	Up to 60 months	Is defined as the percentage of subjects achieving a CR at any time up to 60 months after JCAR017 treatment
Overall Survival (OS)	Up to 60 months	is defined as the time from start of JCAR017 to time of death due to any cause up to 60 months after JCAR017 treatment
Adverse Events (AEs)	Up to 60 months	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.
Duration of Response (DOR) as assessed by PET-CT and/or CT using "The Lugano Classification"	Up to 60 months	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
Progression-Free Survival (PFS) as assessed by PET-CT and/or CT using "The Lugano Classification"	Up to 60 months	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
Pharmacokinetics - Cmax	Up to 60 months	Maximum concentration
European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30)	Up to 24 months	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.

Trial Locations

Locations (59)

Texas Oncology; 🇺🇸 Dallas, Texas, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

UCLA Medical Centre-Santa Monica; 🇺🇸 Santa Monica, California, United States

University Of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Local Institution - 0601; 🇺🇸 Hollywood, Florida, United States

Washington University School Of Medicine; 🇺🇸 Miami, Florida, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Local Institution - 109; 🇺🇸 Niles, Illinois, United States

University Of Iowa; 🇺🇸 Iowa City, Iowa, United States

Cancer Center of Kansas; 🇺🇸 Wichita, Kansas, United States

University of Maryland - Greenebaum Comprehensive Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital - Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Center; 🇺🇸 Detroit, Michigan, United States

Local Institution - 118; 🇺🇸 Detroit, Michigan, United States

Local Institution - 123; 🇺🇸 Morristown, New Jersey, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Novant Health Presbyterian Medical Center; 🇺🇸 Charlotte, North Carolina, United States

Local Institution - 120; 🇺🇸 Fargo, North Dakota, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Providence Cancer Center/Earle A. Chiles Res. Inst.; 🇺🇸 Portland, Oregon, United States

University of Pennsylvania - Perelman Center for Advanced Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Local Institution - 126; 🇺🇸 Pittsburgh, Pennsylvania, United States

Local Institution - 113; 🇺🇸 Sioux Falls, South Dakota, United States

Local Institution - 125; 🇺🇸 Knoxville, Tennessee, United States

The University of Texas - MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University Of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States

Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

Allgemeinen Krankenhaus (AKH) Wien - Medizinische Universitaet Wien; 🇦🇹 Wien, Austria

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Hopital Maisonneuve - Rosemont; 🇨🇦 Montreal, Quebec, Canada

CHRU-Hopital Claude Huriez; 🇫🇷 Lille, France

CHU Montpellier - Hôpital Saint Eloi; 🇫🇷 Montpellier CEDEX 5, France

Hopital Saint Louis; 🇫🇷 Paris Cedex 10, France

Centre Hospitalier Lyon-Sud; 🇫🇷 Pierre-Benite CEDEX, France

Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou; 🇫🇷 Rennes Cedex 02, France

Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE; 🇫🇷 Toulouse, France

Universitaetsklinikum Ulm; 🇩🇪 Ulm, Baden-Wurttemberg, Germany

Local Institution - 504; 🇩🇪 Regensburg, Bayern, Germany

Local Institution - 506; 🇩🇪 Berlin, Germany

Local Institution - 503; 🇩🇪 Karlsruhe, Germany

Local Institution - 505; 🇩🇪 Kiel, Germany

University Hospital Cologne; 🇩🇪 Köln, Germany

LMU Klinikum der Universitat Munchen; 🇩🇪 Munich, Germany

Azienda Ospedaliera Papa Giovanni Xxiii; 🇮🇹 Bergamo, Italy

Local Institution - 302; 🇮🇹 Bologna, Italy

Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale; 🇮🇹 Naples, Italy

Local Institution - 553; 🇯🇵 Sapporo-shi, Hokkaido, Japan

Local Institution - 550; 🇯🇵 Chuo-ku, Tokyo, Japan

Local Institution - 551; 🇯🇵 Minato-ku, Tokyo, Japan

Local Institution - 552; 🇯🇵 Fukuoka, Japan

Local Institution - 352; 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Marañon; 🇪🇸 Madrid, Spain

Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Virgen Del Rocio; 🇪🇸 Sevilla, Spain

Karolinska Hospital; 🇸🇪 Stockholm, Sweden

University College London Hospitals NHS Foundation Trust - University College Hospital; 🇬🇧 London, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom