Idasanutlin, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

PRIMARY OBJECTIVES: I. To determine the maximum tolerated doses (MTD) of idasanutlin and ixazomib (ixazomib citrate) to be used in combination with dexamethasone in patients with relapsed or refractory multiple myeloma with TP53 (17p) deletion. (Phase I) II. To evaluate the confirmed response rate of ixazomib and idasanutlin used in combination with dexamethasone in patients with relapsed or refractory multiple myeloma with TP53 (17p) deletion. (Phase II) SECONDARY OBJECTIVES: I. To describe the toxicities and the confirmed response rate associated with the combination of idasanutlin, ixazomib and dexamethasone. (Phase I) II. To describe the toxicities associated with the combination of idasanutlin, ixazomib and dexamethasone. (Phase II) III. To describe the complete response (CR) and very good partial response (VGPR) rates. (Phase II) IV. To assess progression-free and overall survival. (Phase II) TERTIARY OBJECTIVES: I. Assess murine double minute 2 (MDM2) inhibition in bone marrow plasma cells. II. Identify potential biomarkers associated with response. III. To explore the pharmacodynamic effects of idasanutlin. OUTLINE: This is a phase I, dose-escalation study of idasanutlin and ixazomib citrate followed by a phase II study. Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and idasanutlin PO once daily (QD) on days 1-5 every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive dexamethasone PO on days 1, 8, 15, and 22 every 28 days for 12 courses at the discretion of the treating physician. After completion of study treatment, patients are followed up for 30 days, every 3 months, and then every 6 months.