Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006)
Condition: Lymphoma, Non-Hodgkin; Lymphoma, Nonhodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: lisocabtagene maraleucel
Intervention description: lisocabtagene maraleucel will be administered as a single dose intravenous (IV) injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: JCAR017; lisocabtagene maraleucel; NHL; chimeric antigen receptor; CAR; CAR T cell; autologous T cell therapy; immunotherapy; cell therapy; liso-cel

Summary:

      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.
    

Eligibility criteria:

        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