Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma.

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Kumar SK, Buadi FK, LaPlant B, Halvorson A, Leung N, Kapoor P, Dingli D, Gertz MA, Go RS, Bergsagel PL, Lin Y, Dispenzieri A, Hwa YL, Fonder A, Hobbs M, Fonseca R, Hayman SR, Stewart AK, Lust JA, Mikhael J, Gonsalves W, Reeder C, Skacel T, Rajkumar SV, Lacy MQ

Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma.

Blood Cancer J. 2018 Jul 30;8(8):70. doi: 10.1038/s41408-018-0106-3.

PubMed ID

30061664 [ View in PubMed

]

Abstract

Ixazomib is the first oral proteasome inhibitor to enter the clinic. Given the efficacy of bortezomib in combination with cyclophosphamide and dexamethasone, we studied the combination of ixazomib, cyclophosphamide and dexamethasone (ICd) in newly diagnosed multiple myeloma (NDMM) and patients with measurable disease, irrespective of transplant eligibility, were enrolled. The phase 1 was to determine the maximum tolerated dose (MTD) of cyclophosphamide in the combination. Patients received ixazomib 4 mg (days 1, 8, 15), dexamethasone 40 mg (days 1, 8, 15, 22), and cyclophosphamide 300 or 400 mg/m(2) days 1, 8, 15, 22; cycles were 28 days. We enrolled 51 patients, 10 in phase 1 and 41 patients in phase 2. The median age was 64.5 years (range: 41-88); 29% had high or intermediate risk FISH. The MTD was 400 mg/m(2) of cyclophosphamide weekly. The best confirmed response in all 48 patients included >/= partial response in 77%, including >/= VGPR in 35%; 3 patients had a sCR. The response rate for all 48 evaluable patients at 4-cycles was 71%; the median time to response was 1.9 months. Common adverse events included cytopenias, fatigue and GI intolerance. ICd is a convenient, all oral combination that is well tolerated and effective in NDMM.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Ixazomib	Cytochrome P450 1A2	Protein	Humans	Unknown	Substrate	Details