SMAC Mimetic LCL161 Alone or With Cyclophosphamide in Treating Patients With Relapsed or Refractory Multiple Myeloma

PRIMARY OBJECTIVES: I. To evaluate the confirmed overall response rate (\>= partial response \[PR\]) to LCL161 (SMAC mimetic LCL161), used as a single agent, in patients with relapsed multiple myeloma (MM). SECONDARY OBJECTIVES: I. To estimate the confirmed overall response rate to LCL161 in combination with cyclophosphamide, when cyclophosphamide is added to LCL161 for lack of response or progression. II. To estimate the overall survival and event-free survival of patients treated with LCL161 in combination with cyclophosphamide, when cyclophosphamide is added to LCL161 for lack of response or progression. III. To evaluate the tolerability of LCL161 alone and in combination with cyclophosphamide in patients with relapsed MM. TERTIARY OBJECTIVES: I. To determine degradation of cellular inhibitor of apoptosis protein-1 (cIAP1) in peripheral blood mononuclear cells (PBMC), changes in serum cytokines, and changes in immune cell subsets by flow cytometry. II. To correlate the effect of LCL161 with the presence of activating mutations of the nuclear factor kappa beta (NFKB) pathway. III. To evaluate the pharmacokinetics (PK) of LCL161 alone, and LCL161 in combination with cyclophosphamide. IV. To describe patient-reported health-related quality of life and symptoms. OUTLINE: Patients receive SMAC mimetic LCL161 orally (PO) once daily (QD) on days 1, 8, 15, and 22. Patients lacking a minor response by end of course 2 or partial response by end of course 4 may also receive cyclophosphamide PO QD on days 1, 8, 15, and 22 at the discretion of the treating physician. Patients taking cyclophosphamide with less than a 25% interval reduction in paraprotein receive SMAC mimetic LCL161 on days 2, 9, 16, and 23. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 6 months for 1 year.