Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006)

Purpose

This is a Phase 2, open-label, multicenter study to determine the efficacy and safety of lisocabtagene maraleucel (JCAR017) in adult subjects who have relapsed from, or are refractory to, a single line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) and are ineligible for hematopoietic stem cell transplant (based on age, performance status, and/or comorbidities). Subjects will receive treatment with lisocabtagene maraleucel and will be followed for 2 years for safety, pharmacokinetics and biomarkers, disease status, quality of life, and survival.

Conditions

  • Lymphoma, Non-Hodgkin
  • Lymphoma, Nonhodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Confirmation of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma of the following histology at relapse: diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple hit lymphoma [DHL/THL]), and follicular lymphoma Grade 3B per WHO 2016 classification - Previous treatment must include treatment with a single line of chemoimmunotherapy containing an anthracycline and a CD20-targeted agent - Subjects must be deemed ineligible for both high-dose chemotherapy and hematopoietic stem cell transplant (based on age, performance status and/or comorbidities) while also having adequate organ function for CAR T cell treatment. - Positron emission tomography (PET)-positive disease - Histological confirmation of diagnosis at last relapse. Enough tumor material must be available for central confirmation of diagnosis, otherwise a new tumor biopsy is mandated. - ECOG performance status of 0, or 1, or 2 - Adequate vascular access for leukapheresis procedure (either peripheral line or surgically-placed line) - Subjects must agree to use appropriate contraception - Subjects must agree to not donate blood, organs, semen, and egg cells for usage in other individuals for at least 1 year following lymphodepleting chemotherapy

Exclusion Criteria

  • Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study) - History of another primary malignancy that has not been in remission for at least 2 years. - Previous treatment with CD19-targeted therapy, with the exception of prior lisocabtagene maraleucel treatment in this protocol for subjects receiving retreatment - Active hepatitis B or hepatitis C infection at the time of screening - History of or active human immunodeficiency virus (HIV) infection at the time of screening - Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or lisocabtagene maraleucel administration - History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease - History or presence of clinically relevant CNS pathology - Pregnant or nursing women - Subject does not meet protocol-specified washout periods for prior treatments - Prior hematopoietic stem cell transplant - Progressive vascular tumor invasion, thrombosis, or embolism - Venous thrombosis or embolism not managed on stable regimen of anticoagulation - Uncontrolled medical, psychological, familial, sociological, or geographical conditions

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Treatment 		Lisocabtagene maraleucel at a dose of 100×10^6 CAR+ T cells (50×10^6 CD8+ CAR+ T cells and 50×10^6 CD4+ CAR+ T cells), will be given IV in a single-dose schedule on Day 1 (between 2 and 7 days following the completion of lymphodepleting chemotherapy).
  • Biological: lisocabtagene maraleucel
    lisocabtagene maraleucel will be administered as a single dose intravenous (IV) injection
    Other names:
    • JCAR017
    • liso-cel

Recruiting Locations

More Details

NCT ID
NCT03483103
Status
Completed
Sponsor
Juno Therapeutics, a Subsidiary of Celgene