Dinaciclib, Bortezomib, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

PRIMARY OBJECTIVES: I. To determine the maximally tolerated doses of dinaciclib and bortezomib, when used in combination, in two different schedules, for treatment of relapsed multiple myeloma. SECONDARY OBJECTIVES: I. To determine the toxicities associated with dinaciclib and bortezomib, when used in combination, for treatment of relapsed multiple myeloma. II. To determine the overall response rate associated with dinaciclib and bortezomib, when used in combination, for treatment of relapsed multiple myeloma. III. To explore the differences in toxicity associated with two different schedules of dinaciclib and bortezomib used in combination. TERTIARY OBJECTIVES: I. To examine if expression levels of target cyclin dependent kinase (CDK): CDK 2,5,7 and 9 levels in cluster of differentiation (CD)138-purified tumor cells, will be correlated with response (clinical and molecular) to determine if high or low level target CDK expression, if present, influences dinaciclib efficacy. II. To examine if immunoglobulin (Ig)H translocation status, P53 status and presence of v-myc myelocytomatosis viral oncogene homolog (avian) (Myc) amplification or rearrangement, determined on patient bone marrow before treatment, using a pre validated fluorescence in situ hybridization (FISH) panel to identify common myeloma translocations, will be correlated with molecular and/or clinical markers of drug activity, and to assess if specific genetic subgroups of myeloma tumors are responsive or resistant. III. To determine the gene expression profiles of myeloma cells before and after treatment to understand the role of tumor gene dysregulation and/or dinaciclib induced effects on transcription. OUTLINE: This is a dose-escalation study of dinaciclib and bortezomib. Patients are assigned to 1 of 2 treatment schedules. SCHEDULE I: Patients receive dinaciclib intravenously (IV) over 2 hours and bortezomib subcutaneously (SC) or IV (if patients do not tolerate SC injection) on days 1, 8, and 15 and dexamethasone orally (PO) once daily (QD) on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. SCHEDULE II: Patients receive dinaciclib IV over 2 hours on day 1; bortezomib SC on days 1 and 8; and dexamethasone PO QD on days 1, 2, 8, and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and 3 months.