NCT03744676 - 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) | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3

Cytokine release syndrome is characterized by high fever, fatigue, nausea, headache, dyspnea, tachycardia, rigors, hypotension, hypoxia, myalgia/arthralgia, and anorexia. Incidence of Grade ≥ 3 CRS, based on the TEAE with MedDRA PT "Cytokine release syndrome," graded according to the grading scale adapted from Lee (Lee 2014).

Time frame: From first dose to 90 days following first dose (up to approximately 90 days)

Percentage of Participants With Neurotoxicity (NT) Adverse Events Grade ≥ 3

NT events have also been reported and may include neurologic symptoms such as altered mental status, aphasia, altered level of consciousness, and seizures or seizure-like activity. Incidence of Grade ≥ 3 NT, defined as an Investigator-identified TEAE considered neurotoxicity related to JCAR017.

Time frame: From first dose to 90 days following first dose (up to approximately 90 days)

Percentage of Participants With Infection Adverse Events Grade ≥ 3

Incidence of treatment-emergent Grade ≥ 3 infections, defined using MedDRA SOC.

Time frame: From first dose to 90 days following first dose (up to approximately 90 days)

Percentage of Participants With Grade ≥ 3 Prolonged Cytopenia at Day 29.

Prolonged cytopenia is defined as the occurrence of Grade ≥ 3 cytopenia not resolved by the Day 29 visit, based on laboratory results of low hemoglobin, absolute neutrophil count decreased, and platelet count decreased. The frequency of subjects experiencing each individual laboratory abnormality and the total number with at least 1 abnormality will be summarized, as will recovery from prolonged cytopenia after Day 29.

Time frame: At Day 29 after first treatment

Secondary Outcomes

Number of Participants With Adverse Events

Time frame: From first dose to 90 days following first dose (up to approximately 90 days)

Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology

Time frame: From first dose to up to 41 months

Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry

Time frame: From first dose to up to 41 months

Number of Participants With Adverse Events Grade ≥ 3

Time frame: From first dose to 90 days following first dose (up to approximately 90 days)

Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS)