PRIMARY OBJECTIVES:~I. To determine the maximum tolerated dose of cyclophosphamide that can be combined with ixazomib citrate (ixazomib) and dexamethasone in patients with previously untreated symptomatic multiple myeloma (MM). (Phase I Cohort A) II. To determine the complete plus very good partial response rate (>= VGPR) of ixazomib, used in combination with cyclophosphamide and dexamethasone in patients with previously untreated symptomatic MM. (Phase II Cohort A) III. To determine the hematologic response rate of ixazomib, used in combination with cyclophosphamide and dexamethasone in patients with previously untreated light chain amyloidosis. (Phase II Cohort B)~SECONDARY OBJECTIVES:~I. To determine the progression free survival and overall survival among patients with previously untreated symptomatic MM following treatment with ixazomib in combination with cyclophosphamide and dexamethasone followed by ixazomib maintenance till progression. (Cohort A) II. To determine the toxicities associated with ixazomib in combination with cyclophosphamide and dexamethasone in patients with previously untreated symptomatic MM. (Cohort A) III. To determine the organ response rate of ixazomib, used in combination with cyclophosphamide and dexamethasone in patients with previously untreated light chain amyloidosis. (Cohort B) IV. To determine the progression free survival and overall survival among patients with previously untreated light chain amyloidosis following treatment with ixazomib in combination with cyclophosphamide and dexamethasone followed by Ixazomib maintenance till progression. (Cohort B) V. To determine the toxicities associated with ixazomib in combination with cyclophosphamide and dexamethasone in patients with previously untreated light chain amyloidosis. (Cohort B)~TERTIARY OBJECTIVES:~I. To examine the pharmacokinetics of ixazomib when used in combination with cyclophosphamide and dexamethasone. (Cohort A) II. To assess the incidence of neurotoxicity using patient completed questionnaires. (Cohort A)~OUTLINE: This is a phase I, dose-escalation study of cyclophosphamide followed by a phase II study.~INDUCTION THERAPY: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and cyclophosphamide PO and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.~MAINTENANCE THERAPY: Patients receive ixazomib citrate PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up every 3-6 months for 5 years.
This phase I/II trial studies the side effects and the best dose of cyclophosphamide when given together with ixazomib citrate and dexamethasone in treating patients with previously untreated symptomatic multiple myeloma or light chain amyloidosis. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide together with ixazomib citrate and dexamethasone may be a better treatment for multiple myeloma or light chain amyloidosis.