Description:
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.
Title
- Brief Title: 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, 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)
Clinical Trial IDs
- ORG STUDY ID:
JCAR017-FOL-001
- SECONDARY ID:
U1111-1244-9768
- SECONDARY ID:
2019-004081-18
- NCT ID:
NCT04245839
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Fludarabine | | Administration of JCAR017 |
Cyclophosphamide | | Administration of JCAR017 |
JCAR017 | | Administration of JCAR017 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Administration of JCAR017 | Experimental | 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. | - Fludarabine
- Cyclophosphamide
- JCAR017
|
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Response Rate (ORR) |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | 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
Measure: | Complete response rate (CRR) as assessed but PET-CT and/or CT using "The Lugano Classification" |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | Is defined as the percentage of subjects achieving a CR at any time up to 24 months after JCAR017 treatment |
Measure: | 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 |
Safety Issue: | |
Description: | 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 |
Measure: | Duration of Response (DOR) as assessed by PET-CT and/or CT using "The Lugano Classification" |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | 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 |
Measure: | Progression-Free Survival (PFS) as assessed by PET-CT and/or CT using "The Lugano Classification" |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | 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 |
Measure: | Overall Survival (OS) |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | is defined as the time from start of JCAR017 to time of death due to any cause up to 24 months after JCAR017 treatment |
Measure: | Adverse Events (AEs) |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | 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. |
Measure: | Pharmacokinetics - Cmax |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | Maximum concentration |
Measure: | Pharmacokinetics - Tmax |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | Time to maximum concentration |
Measure: | Pharmacokinetics - AUC |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | Area under the curve |
Measure: | European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30) |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | 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. |
Measure: | Functionality Assessment of Cancer Therapy Lymphoma Subscale (FACT-LymS) |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Celgene |
Trial Keywords
- B-cell Non-Hodgkin Lymphoma (NHL)
- JCAR017
- Relapsed or Refractory
Last Updated
August 9, 2021