A multicenter phase I/II study of obatoclax mesylate administered as a 3- or 24-hour infusion in older patients with previously untreated acute myeloid leukemia.
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An open-label phase I/II study of single-agent obatoclax determined a maximum tolerated dose (MTD) and schedule, safety, and efficacy in older patients (≥ 70 yr) with untreated acute myeloid leukemia (AML).Phase I evaluated the safety of obatoclax infused for 3 hours on 3 consecutive days (3 h × 3 d) in 2-week cycles. Initial obatoclax dose was 30 mg/day (3 h × 3 d; n = 3). Obatoclax was increased to 45 mg/day (3 h × 3 d) if ≤ 1 patient had a dose-limiting toxicity (DLT) and decreased to 20 mg/day (3 h × 3 d) if DLT occurred in ≥ 2 patients. In the phase II study, 12 patients were randomized to receive obatoclax at the dose identified during phase I (3 h × 3 d) or 60 mg/day administered by continuous infusion over 24 hours for 3 days (24 h × 3 d) to determine the morphologic complete response rate.In phase I, two of three patients receiving obatoclax 30 mg/day (3 h × 3 d) experienced grade 3 neurologic DLTs (confusion, ataxia, and somnolence). Obatoclax was decreased to 20 mg/day (3 h × 3 d). In phase II, no clinically relevant safety differences were observed between the 20 mg/day (3 h × 3 d; n = 7) and 60 mg/day (24 h × 3 d; n = 5) arms. Neurologic and psychiatric adverse events were most common and were generally transient and reversible. Complete response was not achieved in any patient.Obatoclax 20 mg/day was the MTD (3 h × 3 d) in older patients with AML. In the schedules tested, single-agent obatoclax was not associated with an objective response. Evaluation in additional subgroups or in combination with other chemotherapy modalities may be considered for future study.ClinicalTrials.gov NCT00684918.
Drug Administration Schedule
Aged, 80 and over
Leukemia, Myeloid, Acute
Published Version (Please cite this version)10.1371/journal.pone.0108694
Publication InfoErba, Harry; Schimmer, Aaron D; Raza, Azra; Carter, Thomas H; Claxton, David; DeAngelo, Daniel J; ... Borthakur, Gautam (2014). A multicenter phase I/II study of obatoclax mesylate administered as a 3- or 24-hour infusion in older patients with previously untreated acute myeloid leukemia. PloS one, 9(10). pp. e108694. 10.1371/journal.pone.0108694. Retrieved from https://hdl.handle.net/10161/19546.
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Instructor in the Department of Medicine
I am a clinical investigator in the Division of Hematologic Malignancies and Cellular Therapy in the Department of Medicine. I serve as Director of the Leukemia Program and Director of Phase I Development in Hematologic Malignancies. I am also the Chair of the SWOG Leukemia Committee. I am interested in the clinical development of novel therapies for acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative neoplasms (such as chronic myeloid leukemia, polycythemia v