This phase I trial studies the best dose and side effects of B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR)-expressing T lymphocytes, cyclophosphamide, and fludarabine with or without lenalidomide in treating patients with multiple myeloma that is increasing in extent or severity (progressive or persistent) or does not respond to treatment (refractory). Combinations of biological substances in BCMA-specific CAR-expressing T lymphocytes may be able to carry cancer-killing substances directly to cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, fludarabine, and lenalidomide, work in different way to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BCMA-specific CAR-expressing T lymphocytes, cyclophosphamide, and fludarabine with lenalidomide may kill more cancer cells.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03070327.
PRIMARY OBJECTIVE:
I. To determine the safety and maximum tolerated dose (MTD) of BCMA-specific CAR-expressing T lymphocytes (EGFRt/BCMA-41BBz CAR T cells) in patients with refractory, persistent, or progressive multiple myeloma (MM) with and without concomitant lenalidomide.
SECONDARY OBJECTIVES:
I. To assess the anti-MM efficacy of adoptively transferred EGFRt/BCMA-41BBz T cells including induction of minimal residual disease (MRD) (paraprotein, 10 marker flow, polymerase chain reaction [PCR]).
II. To quantify persistence and expansion of CAR T cells in peripheral blood (PB) and bone marrow (BM) (flow, PCR).
EXPLORATORY OBJECTIVES:
I. To assess changes in CAR T cell phenotype from apheresis to end of production to post-infusion in patients with MM (flow, gene expression profile [GEP]).
II. To monitor changes in cytokine profiles in serum and BM after adoptive transfer of CAR T cells (Luminex),
III. To monitor soluble BCMA in serum before and after adoptive transfer of T cells (Luminex).
IV. To assess changes in the MM microenvironment after CAR T cell infusion (flow, quantitative immunofluorescence, GEP).
V. To monitor for B cell aplasia or hypogammaglobulinemia after BCMA targeted CAR T cell therapy (flow, quantitate immunoglobulins).
VI. To assess how lenalidomide may impact T cell immunophenotype after CAR T cell production.
OUTLINE: This is a dose-escalation study of BCMA-specific CAR-expressing T lymphocytes. Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive cyclophosphamide intravenously (IV) for 1 dose or cyclophosphamide IV for 3 doses and fludarabine IV for 3 doses between days -2 and -7. Patients receive BCMA-specific CAR-expressing T lymphocytes IV over 5-120 minutes on day 0.
COHORT II: Patients receive cyclophosphamide intravenously (IV) for 1 dose or cyclophosphamide IV for 3 doses and fludarabine IV for 3 doses between days -2 and -7. Beginning day -1, patients receive lenalidomide orally (PO) then continue for up to 21 or 28 days. Patients receive BCMA-specific CAR-expressing T lymphocytes IV over 5-120 minutes on day 0.
After completion of study treatment, patients are followed up weekly for up to 1 month, monthly for 6 months, and then annually for up to 15 years.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorSham Mailankody
