This phase I trial studies the side effects and best dose of BCMA CAR-T cells in treating patients with BCMA positive multiple myeloma that has come back or does not respond to treatment. T cells are a type of white blood cell and a major component of the immune system. T-cells that have been genetically modified in the laboratory express BCMA and may kill cancer cells with the protein BCMA on their surface. Giving chemotherapy before BCMA CAR-T cells may reduce the amount of disease and to cause a low lymphocyte (white blood cell) count in the blood, which may help the infused BCMA CAR-T cells survive and expand.
PRIMARY OBJECTIVE: I. To evaluate the safety of adoptive therapy with ex vivo expanded autologous CD8+ plus CD4+ T cells transduced to express a human B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) for patients with relapsed or treatment refractory multiple myeloma. SECONDARY OBJECTIVES: I. To determine the duration of in vivo persistence and the phenotype of long lived CAR-T cells. II. To determine the degree to which adoptively transferred T cells traffic to multiple myeloma (MM) cells in the bone marrow (BM) and function in vivo. III. To estimate the antitumor activity of adoptively transferred BCMA-specific CAR-expressing T lymphocytes (BCMA CAR-T cells). OUTLINE: This is a dose-escalation study of BCMA-specific CAR-expressing T lymphocytes. Patients undergo leukapheresis to obtain their immune cells, from which CAR-T cells are produced. A few weeks later, patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning 36-96 hours after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes intravenously (IV) over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator). After completion of study treatment, patients are followed up at 60, 90, 120, 180, and 365 days and then annually up to 15 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Given IV
Given IV
Given IV
Undergo leukapheresis
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Dose-limiting Toxicities (DLT) Rate
Observed DLT rates will be summarized based on the DLT-Evaluable analysis set. Outcome will be reported as count of participants in each arm who experienced a DLT. No patients received more than one CAR T cell infusion, so DLT assessment period was only 28 days after first and only CAR T infusion for all patients.
Time frame: Up to 28 days after CAR T cell infusion
Count of Patients That Experienced Adverse Events
Toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 No patients received more than one CAR T cell infusion, so AE assessment period was only 28 days after first and only CAR T infusion for all patients.
Time frame: Up to 28 days after CAR T-cell infusion
Duration of Persistence of Adoptively Transferred BCMA CAR-T Cells
Persistence of CART cells is tested by qPCR in PBMC.
Time frame: Assessed from Baseline up to a maximum of 537 days
Number of Participants With Detectable BCMA CART Cell Migration to Primary Disease Site (Bone Marrow) at Day 28
Time frame: Baseline up to Day 28
Objective Response Rate (ORR)
Number of patients with a best response of either complete response, stringent complete response, very good partial response or partial response, assessed using modified International Myeloma Working group response criteria.
Time frame: Baseline up to 3 months after CART infusion
Progression-free Survival (PFS)
Outcome is reported as the count of participants who were alive at the 1 year post treatment mark and did not experience disease progression by the 1 year post treatment mark.
Time frame: Assessed up to 1 year after CART infusion
Overall Survival (OS)
Outcome is reported as a count of participants who were alive at the 1 year post-infusion timepoint.
Time frame: Assessed up to 1 year after CART infusion
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