A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)
Condition: Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Disorder
MeSH terms: Lymphoma; Neoplasms; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases
Intervention: lisocabtagene maraleucel
Intervention description: lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lisocabtagene maraleucel; liso-cel; JCAR017; relapse; refractory; B-Cell Non-Hodgkin Lymphoma; NHL; chimeric antigen receptor; CAR; CAR T cell; autologous T cell therapy; immunotherapy; cell therapy; B-cell malignancies

Summary:

      This is an open-label, multicenter, Phase 2 study to determine the safety, PK, and efficacy
      of lisocabtagene maraleucel (JCAR017) in subjects who have relapsed from, or are refractory
      to, two lines of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) in the
      outpatient setting. Subjects will receive treatment with JCAR017 and will be followed for up
      to 2 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years at the time of consent

          -  Relapsed or refractory B-cell NHL of the following histologies: diffuse large B cell
             lymphoma (DLBCL) not otherwise specified; includes biopsy-confirmed transformed DLBCL
             from indolent histologies, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6
             rearrangements with DLBCL histology, primary mediastinal B-cell lymphoma(PMBCL), and
             follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline
             and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease
             after at least 2 systemic lines of therapy for DLBCL or after auto-HSCT.

          -  Positron-emission tomography-positive disease by Lugano Classification

          -  Eastern Cooperative Oncology Group performance status of 0 to 1

          -  Adequate bone marrow, renal, hepatic, pulmonary, cardiac organ function

          -  Adequate vascular access for leukapheresis procedure

          -  Subjects who have received previous CD19-targeted therapy must have CD19-positive
             lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy

          -  Subjects must agree to use appropriate contraception.

        Exclusion Criteria:

          -  Subjects with central nervous system (CNS)-only involvement by malignancy (note:
             subjects with secondary CNS involvement are allowed on study)

          -  History of prior allogeneic hematopoietic stem cell transplant

          -  Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with
             fludarabine or cladribine within 3 months of leukapheresis

          -  History of another primary malignancy that has not been in remission for at least 2
             years.The following are examples of exceptions from the 2-year limit: nonmelanoma skin
             cancer, definitively-treated stage 1 solid tumor with a low risk of recurrence,
             curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy
             or a squamous intraepithelial lesion on a Papanicolau smear.

          -  Active hepatitis B or hepatitis C infection at the time of screening

          -  History of or active human immunodeficiency virus infection at the time of screening

          -  Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate
             anti-infection treatment at the time of leukapheresis or lisocabtagene maraleucel
             administration

          -  Presence of acute or chronic graft-versus-host disease

          -  History of clinically significant cardiac conditions within the past 6 months

          -  History or presence of clinically relevant CNS pathology such as epilepsy/seizure,
             paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's
             disease, cerebellar disease, organic brain syndrome, or psychosis

          -  Pregnant or nursing women

          -  Subject does not meet protocol-specified washout periods for certain prior treatments

          -  Prior CAR T-cell or other genetically modified T-cell therapy

          -  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 that do not permit compliance with the protocol; or unwillingness or
             inability to follow the procedures required in the protocol