Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study

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From: Journal of Hematology & Oncology(Vol. 8, Issue 1)
Publisher: BioMed Central Ltd.
Document Type: Report
Length: 5,211 words
Lexile Measure: 1630L

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Abstract :

Background The oral proteasome inhibitor ixazomib is under phase 3 clinical investigation in multiple myeloma (MM) in combination with lenalidomide-dexamethasone. This study was conducted to investigate the pharmacokinetic and safety profiles of ixazomib, administered with lenalidomide-dexamethasone, in East Asian patients with relapsed/refractory MM. Methods Adult patients with measurable disease who had received 1-3 prior lines of therapy received oral ixazomib on days 1, 8, and 15, lenalidomide (25 mg) on days 1-21, and dexamethasone (40 mg) on days 1, 8, 15, and 22, in 28-day cycles. Primary objectives were to characterize ixazomib plasma pharmacokinetics, determine the recommended phase 2/3 dose, and evaluate safety and tolerability. Results Forty-three patients were enrolled. No dose-limiting toxicities were reported for the first six patients receiving ixazomib (4.0 mg), confirming this as the recommended phase 2/3 dose. Ixazomib was rapidly absorbed with a median T.sub.max of 1.5 h on day 1 and 2.0 h on day 15 of cycle 1 and had a geometric mean terminal half-life of 6.1 days. Twenty-one (49 %) patients had at least one drug-related grade [greater than or equai to]3 adverse event (AE); the most common were neutropenia (19 %), diarrhea (14 %), and thrombocytopenia (12 %). Twenty-eight of 43 (65 %) response-evaluable patients had at least a partial response. The recommended phase 2/3 dose for ixazomib was determined to be 4.0 mg. Conclusions The all-oral combination of ixazomib plus lenalidomide-dexamethasone appeared active and well tolerated at 4.0 mg. Consequently, East Asian patients enrolled in phase 3 studies are receiving the same ixazomib dose as patients in other regions. Trial registration This study is registered at NCT01645930. Keywords: Multiple myeloma, Ixazomib, Ethnicity, East Asian, Pharmacokinetics

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Gale Document Number: GALE|A541577977