Work

146: Use of a novel organic arsenic (ZIO-101) after autotransplants for multiple myeloma

Year: 2007

Type: article

Abstract: Background Autotransplants are commonly used to treat multiple myeloma; unfortunately most recipients relapse. Subsequent therapy is often difficult because of limited bone marrow reserve. ZIO-101, a new organic arsenic, is active against human myeloma cell lines in vitro and in scid mice with human myeloma xenografts. ZIO-101 is active in phase-1 trials in multiple myeloma and has little bone marrow toxicity. Because of these features, ZIO-101 is a good candidate for therapy of multiple myeloma after an autotransplant. Method Phase-1 and -2 trials in persons with multiple myeloma. Pharmacokinetic (PK) studies. Subjects N=13. Median age, 57 y (range, 41-78 y); 5 were male. All had advanced myeloma: median N prior therapies, 6 (range, 2-12). 6 received ≥1 prior autotransplants. Dosimetry 4 cohorts received 25 courses of ZIO-101 with a starting dose of 78 mg/me2/d IV and a maximum administered dose (MAD) of 420 mg/me2/d. 2 schedules were studied: (1) daily for 5 consecutive d every 4 w; and (2) twice weekly for 3 w every 4 w. Median N cycles was 2 (range, 1-10). Adverse events at doses < 300 mg/me2/d were modest and there was no clinically-important bone marrow toxicity or QTc-prolongation. Estimated maximum tolerated dose (MTD) is 300-420 mg/me2/d. Activity Activity was seen including subjects receiving a prior autotransplant. Details will be presented. PK Studies at 420 mg/me2/d showed a tmax = 1 h (SD ± 0.9), Cmax = 1.06 μg/mL (SD ± 0.07 μg/mL), t1/2 = 17.8 h (SD ± 1.4 h) and AUC0-∞ = 25.9 μg · h/mL (SD ± 0.8 μg · h/mL). Conclusions ZIO-101 is safe in persons with multiple myeloma at doses ≤300-420 mg/me2/d (MTD) and may be especially useful posttransplant because of modest bone marrow suppression.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2006.12.150