Treatment will consist of 28-days cycles with:~Arm 1 (experimental arm):~Carfilzomib administered iv at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) iv on days 1, 8 and 15.~Dexamethasone at a dose of 20 mg po (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16.~Cyclophosphamide at a dose of 300 mg/m2 iv on days 1, 8 and 15~Arm 2 (control arm):~Carfilzomib administered iv at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) iv on days 1, 8, and 15.~Dexamethasone at a dose of 20 mg po (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16.~Once the first 12 cycles are administered, treatment will be administered on days 1 and 15 of each cycle and the visit and doses on day 8 will be omitted in both study arms.~Patients older than 75 years will receive in both arms carfilzomib at a dose of 56 mg/m2 (20 mg/m2 only in the first infusion) during the cycles 1 and 2. If tolerability is acceptable, the dose could be increased up to 70 mg/m2 since the cycle 3.~Treatments will be administered until progressive disease (PD) or unacceptable toxicity. Carfilzomib and cyclophosphamide will be provided by the sponsor. Dexamethasone may be utilized per a site's standard practice and will not be provided by the sponsor.
This is a multicenter, open label, phase II randomized controlled study that will evaluate the efficacy of carfilzomib and dexamethasone in combination with cyclophosphamide in R/R MM patients.~For this purpose, R/R MM patients that have received 1-3 prior lines of therapy, and who are not primary refractory or refractory to proteasome inhibitors will be randomized to receive:~Experimental arm: carfilzomib at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) intravenously (iv) on days 1, 8, and 15, dexamethasone by mouth (po) at a dose of 20 mg (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16 and cyclophosphamide at a dose of 300 mg/m2 iv on days 1, 8 and 15, in 28 days cycles; or~Control arm: the same treatment but without cyclophosphamide.~Once the first 12 cycles are administered, treatment will be administered on days 1 and 15 of each cycle and the visit and doses on day 8 will be omitted in both study arms.~Patients older than 75 years will receive in both arms carfilzomib at a dose of 56 mg/m2 (20 mg/m2 only in the first infusion) during the cycles 1 and 2. If tolerability is acceptable, the dose could be increased up to 70 mg/m2 since the cycle 3.~Treatment will be continued until progression, unacceptable toxicity or investigator or patient decision.