Multiple Myeloma Clinical Trial
Official title:
Phase I Clinical Trial of Bcl2 Inhibitor Venetoclax in Combination With Lenalidomide and Dexamethasone (Ven-Rd), Daratumumab and Dexamethasone (Ven-Dd), or Daratumumab-Lenalidomide-Dexamethasone (Ven-DRd) in t(11;14) Multiple Myeloma
This phase I trial tests the safety, side effects, and best dose of venetoclax in combination with lenalidomide and dexamethasone, daratumumab and dexamethasone, or daratumumab, lenalidomide, and dexamethasone in treating patients with multiple myeloma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Lenalidomide is a drug that is similar to thalidomide, and is used to treat multiple myeloma and certain types of anemia. Lenalidomide belongs to the family of drugs called angiogenesis inhibitors. 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. 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. Adding venetoclax to the other drug combinations may allow control of the cancer than is possible with the current treatments.
PRIMARY OBJECTIVE: I. To estimate the recommended phase II dose (RP2D) of venetoclax that can be combined with standard dose daratumumab and dexamethasone (Dd) (Arm A), lenalidomide and dexamethasone (Rd) (Arm B) or daratumumab, lenalidomide and dexamethasone (DRd) (Arm C) in patients with t(11;14) multiple myeloma (MM). SECONDARY OBJECTIVES: I. To assess frequency and severity of treatment-emergent adverse events (TEAEs) graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. II. To assess best response while on treatment per International Myeloma Working Group (IMWG) criteria. EXPLORATORY OBJECTIVE: I. To examine the effect of treatment on patient reported toxicity and quality of life using validated tools. OUTLINE: This is a dose-escalation study of venetoclax. Patients with relapsed MM (Group 1) are assigned to Arm B or C. Patients with newly diagnosed MM (Group 2) are assigned to Arm A, B, or C. ARM A: Patients receive venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle, daratumumab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, whole-body low-dose computed tomography (WBLDCT), positron emission tomography (PET)/computed tomography (CT) or magnetic resonance imaging (MRI) scans during screening and on study, and bone marrow aspiration and biopsy during screening, and during follow-up ARM B: Patients receive venetoclax PO QD on days 1-28 of each cycle, lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, and during follow-up. ARM C: Patients receive venetoclax PO QD on days 1-28 of each cycle, daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, on study, and during follow-up. After completion of study treatment, patients are followed up at 30 days and then every 3 or 6 months for a total of 3 years. ;
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