Phase I/II Open Label Study of Belumosudil Mesylate Alone, and in Combination With Dexamethasone, in Patients With Relapsed/Refractory Multiple Myeloma

Phase 1 is to find the recommended dose of belumosudil mesylate that can be given to patients with relapsed/refractory MM. Phase 2 is to learn if the dose of belumosudil mesylate found in Phase 1 can help to control the disease.

Primary Objectives: * In Phase I, define the toxicities and recommended Phase II dose (RP2D) of belumosudil mesylate in a population of patients with relapsed/refractory multiple myeloma. * In Phase II, obtain preliminary evidence of efficacy of belumosudil mesylate and further expand the safety experience in this patient population. The overall response rate (ORR) will be defined using the International Myeloma Working Group Uniform Response Criteria as the proportion of patients who, on an intent-to-treat basis, achieve at least a partial response (PR) or better on either belumosudil mesylate alone, or with dexamethasone. * In Phase II, obtain preliminary evidence of efficacy of the combination of belumosudil mesylate with dexamethasone, with the ORR defined as above. Secondary Objectives: * Examine the clinical benefit response rate (CBR), defined as patients experiencing at least a minimal response (MR) or better on belumosudil mesylate alone, and on belumosudil mesylate with dexamethasone. * Examine the disease stabilization rate (DSR), defined as patients experiencing at least stable disease (SD) or better on belumosudil mesylate alone, and on belumosudil mesylate with dexamethasone. * Determine durability of responses to single agent belumosudil mesylate, and/or in combination with dexamethasone, including the progression free survival (PFS), minimal residual disease (MRD) negativity in patients achieving a very good partial remission (VGPR) or complete response (CR), duration of response (DOR), and time to next treatment (TTNT). * Compare the MRD, response, and durability of therapy in patients with standard- and high-risk disease defined by FISH. * Evaluate the impact of therapy and symptom burden with single agent belumosudil mesylate alone, and of belumosudil mesylate with dexamethasone, on patients with relapsed/refractory multiple myeloma on patient-reported outcomes using the European Organization for Research on the Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (QLQ-C30). Exploratory/Correlative Study Objectives: * The baseline bone marrow sample will be separated into CD138+ and CD138- fractions, and the former will be examined by single cell RNA sequencing (scRNA-Seq) and singe cell B-cell receptor sequencing (scBCR-Seq). Also, the CD138- fraction will be examined by scRNA-Seq, scBCR-Seq, and singe cell T-cell receptor sequencing (scTCR-Seq). Our exploratory objectives are to characterize the myeloma cell's transcriptomic profile, including expression levels of ROCK1 and ROCK2, as well as activation status of the IL-6 pathway to then correlate these to any responses that will be seen. * The pre-Cycle 3 bone marrow sample will be similarly processed and analyzed. Our exploratory objectives here will be to characterize the transcriptional changes induced by belumosudil mesylate in the myeloma cells themselves, and also the change in the tumor microenvironment (TME), including in the infiltration by, and activation status of immune effector cells. * Correlate Th17 and regulatory T-cell activation and interleukin level (IL-4, IL6-, IL-17, IL-21, IL-22, and IL-23) changes in myeloma. * To explore the utility of a CMMC assay in monitoring myeloma disease burden and response kinetics. * To explore the potential of MicroOrganoSphereTM (MOS) technology to predict clinical