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

NCT04245839

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.

Related Conditions:
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
FludarabineAdministration of JCAR017
CyclophosphamideAdministration of JCAR017
JCAR017Administration 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

NameTypeDescriptionInterventions
Administration of JCAR017ExperimentalSubjects 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 or two prior lines of systemic therapy are eligible if they
             present with high risk features. Patients that received three 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)

          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 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 T-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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response Rate (CRR)
Time Frame:Up to 24 months
Safety Issue:
Description:is defined as the percentage of subjects achieving a 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:Overall response rate (ORR) 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 percentage of subjects achieving a response (CR or PR) 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

July 21, 2020