Allogeneic ORCA-Q Stem Cell Transplant for the Treatment of Relapsed and Refractory High Risk Multiple Myeloma

PRIMARY OBJECTIVE: I. To evaluate the safety of allogeneic ORCA-Q transplantation in subjects with R/R multiple myeloma with high-risk features. SECONDARY OBJECTIVES: I. To evaluate the efficacy of allogeneic ORCA-Q transplantation in subjects with R/R multiple myeloma with high-risk features. II. To further evaluate the safety of allogeneic ORCA-Q transplantation in subjects with R/R multiple myeloma with high-risk features. EXPLORATORY OBJECTIVE: I. To further evaluate the efficacy of allogeneic ORCA-Q transplantation in subjects with R/R multiple myeloma with high-risk features. OUTLINE: DONORS: Donors receive granulocyte colony-stimulating factor (G-CSF) or filgrastim subcutaneously (SC) daily (QD) on days -6 to -3 and undergo apheresis on day -2 or -1. Donors may also undergo a second apheresis on day -1 or 0. Additionally, donors undergo blood sample collection at screening. PATIENTS: Patients receive thiotepa intravenously (IV) over 3 hours on days -7 and -6, busulfan IV over 3 hours on days -5 to -3, fludarabine IV over 30 minutes on days -5 to -2, Orca-Q prime IV on day 0 followed by Orca-Q supplement IV on day 0 or 1 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo echocardiography or multigated acquisition scan (MUGA) and optional positron emission tomography (PET)/computed tomography (CT) or CT at screening and urine and blood sample collection, as well as bone marrow aspiration and biopsy throughout the study. After completion of study treatment, patients are followed up on days 1-7, 14, 21, 30, 60, 90, 180, and 365.