Donor Immune Cells (TGFbi NK Cells) and Isatuximab for the Treatment of Relapsed or Refractory Multiple Myeloma

PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of transforming growth factor beta imprinted natural killer cells (TiNK) and isatuximab in patients with multiple myeloma (MM) relapsed or refractory (R/R) to BCMA-targeting therapy. SECONDARY OBJECTIVES: I. To evaluate the objective response rate (ORR) by International Myeloma Working Group (IMWG) criteria of TiNK and isatuximab in patients with MM R/R to BCMA-targeting therapy. II. To determine the time to response (TTR), time to next therapy (TTNT), the duration of response (DOR), progression free survival (PFS), and overall survival (OS) at 1 year. III. To determine correlatives of outcomes. IV. To assess quality of life (QOL) with therapy. OUTLINE: This is a dose-escalation study of TiNK followed by a dose-expansion study. Patients receive cyclophosphamide intravenously (IV) on day 1, dexamethasone orally (PO) on days 1-4, TiNK IV on day 8, and isatuximab IV on days 8 and 15 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy during screening and on study, as well as optionally during follow up. Patients undergo echocardiography (ECHO) during screening and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days, 60 days. Patients who discontinue study treatment for reasons other than progressive disease follow up every 12 weeks for up to 2 years.