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

Lymphoma, Non-Hodgkin Clinical Trial

— TRANSCEND FL  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04245839
• Other study ID #: JCAR017-FOL-001
• Secondary ID: U1111-1244-97682
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 14, 2020
• Est. completion date: September 28, 2028

Study information

• Verified date: November 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 213
• Est. completion date: September 28, 2028
• Est. primary completion date: September 28, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Fludarabine
Fludarabine
• Cyclophosphamide
Cyclophosphamide
• JCAR017
JCAR017

Locations

Country	Name	City	State
Austria	Local Institution - UNK-201	Salzburg
Austria	Local Institution - 450	Wien
Canada	Local Institution - 151	Montreal	Quebec
Canada	Local Institution - 150	Toronto	Ontario
France	Local Institution - 252	Lille
France	Local Institution - 251	Montpellier CEDEX 5
France	Local Institution - 250	Pierre-Benite CEDEX
Germany	Local Institution - 501	Köln
Germany	Local Institution - 502	Munich
Germany	Local Institution - 500	Ulm
Italy	Local Institution - 300	Bergamo
Italy	Local Institution - 301	Naples
Japan	Local Institution - 550	Chuo-ku	Tokyo
Japan	Local Institution - 552	Fukuoka
Japan	Local Institution - 551	Minato-ku	Tokyo
Japan	Local Institution - 553	Sapporo-shi	Hokkaido
Spain	Local Institution - 350	Salamanca
Spain	Local Institution - 351	Sevilla
Sweden	Local Institution - 600	Stockholm
United Kingdom	Local Institution - 200	London
United Kingdom	Local Institution - 201	Manchester
United States	Local Institution - 107	Aurora	Colorado
United States	Local Institution - 102	Baltimore	Maryland
United States	Local Institution - 100	Boston	Massachusetts
United States	Local Institution - 101	Boston	Massachusetts
United States	Local Institution - 110	Charlotte	North Carolina
United States	Local Institution - 115	Charlottesville	Virginia
United States	Local Institution - 103	Chicago	Illinois
United States	Local Institution - 112	Cleveland	Ohio
United States	Local Institution - 104	Houston	Texas
United States	Local Institution - 105	New Haven	Connecticut
United States	Local Institution - 116	New York	New York
United States	Local Institution - 109	Niles	Illinois
United States	Local Institution - 117	Philadelphia	Pennsylvania
United States	Local Institution - 114	Portland	Oregon
United States	Local Institution - 111	Santa Monica	California
United States	Local Institution - 108	Seattle	Washington
United States	Local Institution - 113	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Austria,  Canada,  France,  Germany,  Italy,  Japan,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Pharmacokinetics - Cmax	Maximum concentration	Up to 60 months
Secondary	Pharmacokinetics - Tmax	Time to maximum concentration	Up to 60 months
Secondary	Pharmacokinetics - AUC	Area under the curve	Up to 60 months
Secondary	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
Secondary	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

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