A Study to Evaluate the Efficacy and Safety of JCAR017 in Adult Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma (NHL)
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT04245839 Recruiting January 29, 2020 November 16, 2021

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: Lymphoma, Non-Hodgkin
Intervention/treatment: Drug: Fludarabine
Drug: Cyclophosphamide
Drug: JCAR017
Phase: Phase 2
Detailed Description

N/A


study design
Study Type: Interventional
Estimated Enrollment : 188 participants
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: July 2020
Estimated Primary Completion Date: April 2024
Estimated Study Completion Date: April 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
outcome measures
Primary Outcome Measures: 1. Overall Response Rate (ORR) [ Time Frame: 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: 1. Complete response rate (CRR) as assessed but PET-CT and/or CT using "The Lugano Classification" [ Time Frame: Up to 24 months ]
Is defined as the percentage of subjects achieving a CR at any time up to 24 months after JCAR017 treatment
2. Duration of Response (DOR) if Best Overall Response (BOR) is CR, as assessed by PET-CT and/or CT using "The Lugano Classification" [ Time Frame: 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
3. Duration of Response (DOR) as assessed by PET-CT and/or CT using "The Lugano Classification" [ Time Frame: 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
4. Progression-Free Survival (PFS) as assessed by PET-CT and/or CT using "The Lugano Classification" [ Time Frame: 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
5. Overall Survival (OS) [ Time Frame: 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
6. Adverse Events (AEs) [ Time Frame: 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.
7. Pharmacokinetics - Cmax [ Time Frame: Up to 24 months ]
Maximum concentration
8. Pharmacokinetics - Tmax [ Time Frame: Up to 24 months ]
Time to maximum concentration
9. Pharmacokinetics - AUC [ Time Frame: Up to 24 months ]
Area under the curve
10. European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30) [ Time Frame: 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.
11. Functionality Assessment of Cancer Therapy Lymphoma Subscale (FACT-LymS) [ Time Frame: 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
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria

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
Contacts

Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com

Contact: First line of the email MUST contain NCT # and Site #.

Locations
United States, California UCLA Medical Centre-Santa Monica Santa Monica
United States, Colorado University of Colorado Cancer Center Aurora
United States, Connecticut Yale New Haven Health - Smilow Cancer Hospita New Haven
United States, Illinois Northwestern University - Robert H. Lurie Comprehensive Cancer Center Chicago
United States, Illinois Illinois Cancer Specialists - Arlington Heights Niles
United States, Maryland University of Maryland - Greenebaum Comprehensive Cancer Center Baltimore
United States, Massachusetts Massachusetts General Hospital - Dana-Farber Cancer Institute (The Jon and JoAnn Hagler Center for Lymphoma) Boston
United States, Massachusetts Beth Israel Deaconess Medical Center Boston
United States, New York Memorial Sloan Kettering Cancer Center New York
United States, North Carolina Novant Health Cancer Specialists Charlotte Charlotte
United States, Ohio Cleveland Clinic - Taussig Cancer Institute Cleveland
United States, Oregon Providence Cancer Center - Earle A. Chiles Research Institute Portland
United States, Pennsylvania Perelman Center for Advanced Medicine - Abramson Cancer Center University of Pennsylvania Philadelphia
United States, South Dakota Avera Research Institute Sioux Falls
United States, Texas The University of Texas - MD Anderson Cancer Center Houston
United States, Virginia University of Virginia Health System Charlottesville
United States, Washington Fred Hutchinson Cancer Research Center Seattle
Austria Allgemeinen Krankenhaus (AKH) Wien - Medizinische Universitaet Wien Wien
Canada, Montreal Hospital Maisonneuve - Rosemont Quebec
Canada, Toronto Princess Margaret Cancer Centre Ontario
Canada CIUSSS de l'Est-de-l'Ile-de-Montreal - Installation Hopital Maisonneuve-Rosemont Quebec
France CHRU-Hopital Claude Huriez Lille
France CHU Montpellier - Hôpital Saint Eloi Montpellier
France Centre Hospitalier Lyon-Sud Pierre-Benite
Germany Universitatsklinikum Koeln Koeln
Germany LMU Klinikum der Universitat Muenchen Munich
Germany Universitaetsklinikum Ulm Ulm
Italy Azienda Ospedaliera Papa Giovanni XXIII Bergamo
Italy Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale Naples
Japan National Cancer Center Hospital Chuo-ku
Japan Kyushu University Hospital Fukuoka
Japan Toranomon Hospital Minato-ku
Japan Hokkaido University Hospital Sapporo-shi, Hokkaido
Spain Universitario de Salamanca - Hospital Clinico Salamanca
Spain Hospital Universitario Virgen del Rocio Sevilla
Sweden Karolinska University Hospital Stockholm
United Kingdom University College London Hospitals NHS Foundation Trust - University College Hospital London
United Kingdom The Christie NHS Foundation Trust Withington
Sponsors and Collaborators
Celgene
Investigator
Study Director : Thalia Farazi, M.D./Ph.D Celgene Medical Director
More Information
Responsible Party : Celgene
ClinicalTrials.gov Identifier : NCT04245839     
Other Study ID Numbers : JCAR017-FOL-001, U1111-1244-9768, 2019-004081-18
First Posted : January 29, 2020
Last Update Posted : November 16, 2021
Last Verified : November 2021
Individual Participant
Data (IPD) Sharing
Statement:
 
Plan to Share IPD: Yes
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/
Supporting Materials: Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene: B-cell Non-Hodgkin Lymphoma (NHL)
JCAR017
Relapsed or Refractory
Additional relevant MeSH terms :
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases