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

Sponsor

Celgene (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04245839

Collaborator

(none)

188

Enrollment

Locations

Arm

48.1

Anticipated Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 2 years.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin	Drug: Fludarabine Drug: Cyclophosphamide Drug: JCAR017	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

188 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 14, 2020

Anticipated Primary Completion Date :

Jul 17, 2024

Anticipated Study Completion Date :

Jul 17, 2024

Arms and Interventions

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 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

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 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

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [Up to 24 months]
Is defined as the percentage of participants achieving either a partial response (PR) or complete response (CR) at any time up to 24 months after JCAR017 treatment as assessed by PET-CT and/or CT using "The Lugano classification"

Secondary Outcome Measures

Complete response rate (CRR) as assessed but PET-CT and/or CT using "The Lugano Classification" [Up to 24 months]
Is defined as the percentage of subjects achieving a CR at any time up to 24 months after JCAR017 treatment
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 24 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 24 months after JCAR017 treatment
Duration of Response (DOR) as assessed by PET-CT and/or CT using "The Lugano Classification" [Up to 24 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 24 months after JCAR017 treatment
Progression-Free Survival (PFS) as assessed by PET-CT and/or CT using "The Lugano Classification" [Up to 24 months]
is defined as the time from start of JCAR017 to disease progression or death from any cause, whichever occurs first up to 24 months after JCAR017 treatment
Overall Survival (OS) [Up to 24 months]
is defined as the time from start of JCAR017 to time of death due to any cause up to 24 months after JCAR017 treatment
Adverse Events (AEs) [Up to 24 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.
Pharmacokinetics - Cmax [Up to 24 months]
Maximum concentration
Pharmacokinetics - Tmax [Up to 24 months]
Time to maximum concentration
Pharmacokinetics - AUC [Up to 24 months]
Area under the curve
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
Patients should have received at least one prior therapy that includes anti-CD20 and alkylating agent
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)
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
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate organ function
Adequate vascular access for leukapheresis procedure

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Centre-Santa Monica	Santa Monica	California	United States	90095
2	UCLA Medical Centre-Santa Monica	Santa Monica	California	United States	90404
3	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
4	Yale New Haven Health - Smilow Cancer Hospita	New Haven	Connecticut	United States	06510
5	Northwestern University - Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois	United States	60611
6	Illinois Cancer Specialists - Arlington Heights	Niles	Illinois	United States	60714
7	University of Maryland - Greenebaum Comprehensive Cancer Center	Baltimore	Maryland	United States	21201
8	Massachusetts General Hospital - Dana-Farber Cancer Institute (The Jon and JoAnn Hagler Center for Lymphoma)	Boston	Massachusetts	United States	02114
9	Massachusetts General Hospital - Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02114
10	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
11	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
12	Novant Health Cancer Specialists Charlotte	Charlotte	North Carolina	United States	28204
13	Cleveland Clinic - Taussig Cancer Institute	Cleveland	Ohio	United States	44195
14	Providence Cancer Center - Earle A. Chiles Research Institute	Portland	Oregon	United States	97213
15	Perelman Center for Advanced Medicine - Abramson Cancer Center University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
16	Avera Research Institute	Sioux Falls	South Dakota	United States	57105
17	The University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
18	University of Virginia Health System	Charlottesville	Virginia	United States	22908
19	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
20	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
21	Allgemeinen Krankenhaus (AKH) Wien - Medizinische Universitaet Wien	Wien		Austria	1090
22	Hospital Maisonneuve - Rosemont	Quebec	Montreal	Canada	H1T 2M4
23	Princess Margaret Cancer Centre	Ontario	Toronto	Canada	M5G 2M9
24	CIUSSS de l'Est-de-l'Ile-de-Montreal - Installation Hopital Maisonneuve-Rosemont	Quebec		Canada
25	CHRU-Hopital Claude Huriez	Lille		France	59037
26	CHU Montpellier - Hôpital Saint Eloi	Montpellier		France	34295
27	Local Institution - 250	Pierre-Benite CEDEX		France	69495
28	Centre Hospitalier Lyon-Sud	Pierre-Benite		France	69495
29	Universitatsklinikum Koeln	Koeln		Germany	50937
30	LMU Klinikum der Universitat Muenchen	Munich		Germany	81377
31	Universitaetsklinikum Ulm	Ulm		Germany	89081
32	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo		Italy	24127
33	Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale	Naples		Italy	80131
34	Local Institution - 301	Naples		Italy	80131
35	Local Institution - 550	Chuo-ku	Tokyo	Japan	104-0045
36	National Cancer Center Hospital	Chuo-ku		Japan	105-8470
37	Kyushu University Hospital	Fukuoka		Japan	812-8582
38	Toranomon Hospital	Minato-ku		Japan	812-8582
39	Hokkaido University Hospital	Sapporo-shi, Hokkaido		Japan	060-8648
40	Universitario de Salamanca - Hospital Clinico	Salamanca		Spain	37007
41	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
42	Karolinska University Hospital	Stockholm		Sweden	S- 141 86
43	University College London Hospitals NHS Foundation Trust - University College Hospital	London		United Kingdom	NW1 2PG
44	The Christie NHS Foundation Trust	Withington		United Kingdom	M20 4BX