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.
Abstract
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.
Type
Journal articleSubject
NeutrophilsHumans
Blast Crisis
Pyrroles
Platelet Count
Treatment Outcome
Drug Administration Schedule
Demography
Aged
Aged, 80 and over
Female
Male
Leukemia, Myeloid, Acute
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https://hdl.handle.net/10161/19546Published Version (Please cite this version)
10.1371/journal.pone.0108694Publication Info
Schimmer, Aaron D; Raza, Azra; Carter, Thomas H; Claxton, David; Erba, Harry; 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Harry Paul Erba
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

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