A Phase I Study of ABT-888 in Combination With Topotecan Plus Carboplatin for High-Risk Myeloproliferative Disorders and AML Out of Myeloproliferative Disorders
I. To determine the feasibility, tolerability, and toxicities of ABT-888 (veliparib) when
administered alone and in combination with topotecan hydrochloride with or without
carboplatin in patients with relapsed or refractory acute leukemia, high-risk
myelodysplasia, or aggressive myeloproliferative disorders.
II. To determine the maximum tolerated dose of ABT-888 when administered with topotecan
hydrochloride and carboplatin in these patients.
III. To determine if ABT-888 when administered with topotecan hydrochloride and carboplatin
can induce clinical responses in these patients.
I. To determine the pharmacokinetics of ABT-888 when administered alone and in combination
with topotecan hydrochloride with or without carboplatin in these patients.
II. To obtain pharmacodynamic data regarding the ability of ABT-888 to inhibit poly
(ADP-ribose) levels in leukemic blasts.
III. To obtain descriptive data regarding the mutational status and/or methylation status of
key genes in selected DNA repair pathways (Fanconi complementation groups A-F, Blooms, and
ataxia-telangiectasia) in leukemic blasts.
OUTLINE: This is a multicenter, dose-escalation study of veliparib.
Patients receive veliparib orally twice daily on days 1-8, 1-14, or 1-21 and topotecan
hydrochloride with or without carboplatin IV continuously over 120 hours on days 3-7.
Treatment repeats every 28-63 days for up to 6 courses in the absence of disease progression
or unacceptable toxicity.
Patients undergo blood sample collection periodically for pharmacokinetic studies.
After completion of study therapy, patients are followed for 30 days.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of veliparib, determined as the highest dose level where 0/3 or 1/6 experience DLT, measured according to NCI-CTCAE 4.0
Up to 63 days
Johns Hopkins University
United States: Food and Drug Administration
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