Selvigaltin With Standard of Care Treatment for the Treatment of Relapsed/Refractory Multiple Myeloma

Overview

This phase I trial studies the side effects and best dose of selvigaltin when given together with standard of care treatment (daratumumab-hyaluronidase, carfilzomib, dexamethasone) in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Selvigaltin works by blocking the activity of a protein called galectin-3. Galectin-3 is involved in various cellular processes, including inflammation and tissue scarring, which is associated with worse outcomes in several forms of cancer. By blocking the activity of galectin-3, selvigaltin may help reduce inflammation and tissue scarring. Daratumumab-hyaluronidase is a drug composed of daratumumab and hyaluronidase. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Hyaluronidase helps deliver the daratumumab to CD38-expressing cancer cells. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving selvigaltin with standard of care treatment may be safe, tolerable, and/or effective in treating patients with relapsed or refractory multiple myeloma.

PRIMARY OBJECTIVES: I. To assess the safety and tolerability of selvigaltin in combination with standard of care treatment regimen (daratumumab, carfilzomib, and dexamethasone) for relapsed/refractory multiple myeloma (RRMM). II. Determine the maximal tolerated dose (MTD) of selvigaltin in combination with a standard of care treatment regimen (daratumumab, carfilzomib, and dexamethasone) for RRMM. SECONDARY OBJECTIVES: I. To collect safety and preliminary efficacy data. II. Rate of bone marrow measurable residual disease (MRD) negativity. EXPLORATORY OBJECTIVE: I. To assess the effects of the combination treatment on the tumor microenvironment (TME) and on immune cell subsets in the peripheral blood and bone marrow. OUTLINE: This is a dose-escalation study of selvigaltin in combination with daratumumab and recombinant human hyaluronidase (daratumumab-hyaluronidase), carfilzomib, and dexamethasone followed by a dose-expansion study. Patients receive selvigaltin orally (PO) twice daily (BID) on days 1-28 of each cycle, daratumumab-hyaluronidase subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2 and days 1 and 15 of cycles 3-6, carfilzomib intravenously (IV) over 30 minutes on days 1, 8, and 15 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who respond to treatment may optionally continue to receive treatment beyond 6 cycles with selvigaltin PO BID on days 1-28 of each cycle, daratumumab-hyaluronidase SC on day 1 of each cycle, carfilzomib IV over 30 minutes on days 1, 8, and 15 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and blood sample collection and bone marrow aspiration and biopsy throughout the trial. Patients also undergo positron emission tomography (PET)/computed tomography (CT), magnetic resonance imaging (MRI), and/or CT during screening and optionally during 1 year follow up. After completion of study treatment, patients that remain on treatment beyond 6 cycles are followed up monthly until disease progression and then every 3 months for up to 3 years. Patients that do not continue treatment are followed up at 30 days and then every 3 months for up to 3 years or until start of a new treatment, disease progression, or death, whichever occurs first.