Clinical trial NCT04245839: A Study to Evaluate the Efficacy and Safety of JCAR017 in Adult Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma (NHL)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin
Keywords: B-cell Non-Hodgkin Lymphoma (NHL)
JCAR017
Relapsed or Refractory
Follicular Lymphoma
Marginal Zone Lymphoma
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2020-01-29
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 60 months
Secondary outcomes:
measure: Complete response rate (CRR) as assessed but PET-CT and/or CT using "The Lugano Classification"
timeFrame: Up to 60 months
measure: Duration of Response (DOR) if Best Overall Response (BOR) is CR, as assessed by PET-CT and/or CT using "The Lugano Classification"
timeFrame: Up to 60 months
measure: Duration of Response (DOR) as assessed by PET-CT and/or CT using "The Lugano Classification"
timeFrame: Up to 60 months
measure: Progression-Free Survival (PFS) as assessed by PET-CT and/or CT using "The Lugano Classification"
timeFrame: Up to 60 months
measure: Overall Survival (OS)
timeFrame: Up to 60 months
measure: Adverse Events (AEs)
timeFrame: Up to 60 months
measure: Pharmacokinetics - Cmax
timeFrame: Up to 60 months
measure: Pharmacokinetics - Tmax
timeFrame: Up to 60 months
measure: Pharmacokinetics - AUC
timeFrame: Up to 60 months
measure: European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30)
timeFrame: Up to 24 months
measure: Functionality Assessment of Cancer Therapy Lymphoma Subscale (FACT-LymS)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Medical Centre-Santa Monica
state: California
city: Aurora
country: United States
facility: University Of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Hollywood
country: United States
facility: Local Institution - 0601
state: Florida
city: Miami
country: United States
facility: Washington University School Of Medicine
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Niles
country: United States
facility: Local Institution - 109
state: Illinois
city: Iowa City
country: United States
facility: University Of Iowa
state: Iowa
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland - Greenebaum Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital - Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Local Institution - 118
state: Michigan
city: Morristown
country: United States
facility: Local Institution - 123
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Fargo
country: United States
facility: Local Institution - 120
state: North Dakota
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Center/Earle A. Chiles Res. Inst.
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania - Perelman Center for Advanced Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution - 126
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Local Institution - 113
state: South Dakota
city: Knoxville
country: United States
facility: Local Institution - 125
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas - MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University Of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Wien
country: Austria
facility: Allgemeinen Krankenhaus (AKH) Wien - Medizinische Universitaet Wien
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve - Rosemont
state: Quebec
city: Lille
country: France
facility: CHRU-Hopital Claude Huriez
city: Montpellier CEDEX 5
country: France
facility: CHU Montpellier - Hôpital Saint Eloi
city: Paris Cedex 10
country: France
facility: Hopital Saint Louis
city: Pierre-Benite CEDEX
country: France
facility: Centre Hospitalier Lyon-Sud
city: Rennes Cedex 02
country: France
facility: Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden-Wurttemberg
city: Regensburg
country: Germany
facility: Local Institution - 504
state: Bayern
city: Berlin
country: Germany
facility: Local Institution - 506
city: Karlsruhe
country: Germany
facility: Local Institution - 503
city: Kiel
country: Germany
facility: Local Institution - 505
city: Köln
country: Germany
facility: University Hospital Cologne
city: Munich
country: Germany
facility: LMU Klinikum der Universitat Munchen
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni Xxiii
city: Bologna
country: Italy
facility: Local Institution - 302
city: Naples
country: Italy
facility: Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale
city: Sapporo-shi
country: Japan
facility: Local Institution - 553
state: Hokkaido
city: Chuo-ku
country: Japan
facility: Local Institution - 550
state: Tokyo
city: Minato-ku
country: Japan
facility: Local Institution - 551
state: Tokyo
city: Fukuoka
country: Japan
facility: Local Institution - 552
city: Barcelona
country: Spain
facility: Local Institution - 352
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Virgen Del Rocio
city: Stockholm
country: Sweden
facility: Karolinska Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust - University College Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: