A Phase 1b/2a Study of ABT-888 in Combination With Bendamustine +/- Rituximab in Lymphoma, Multiple Myeloma and Solid Tumors
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose (MTD) of veliparib (ABT-888) in combination with
bendamustine hydrochloride in patients with solid tumors, lymphoma, or multiple myeloma.
(Phase I) II. To establish the safety of ABT-888 in combination with bendamustine
hydrochloride and rituximab in an expansion cohort of patients with non-Hodgkin lymphoma
(NHL). (Phase I) III. To assess the toxicity profile of this regimen in the above patients.
(Phase I) IV. To determine the complete response (CR) rate in patients with indolent NHL or
mantle cell lymphoma (MCL) treated with ABT-888, bendamustine, and rituximab. (Phase II)
SECONDARY OBJECTIVES:
I. To assess response rates and survival parameters of patients treated with ABT-888,
bendamustine hydrochloride, and with or without rituximab. (Phase I) II. To assess
pharmacokinetic parameters of ABT-888 in this regimen. (Phase I) III. To assess
pharmacodynamic endpoints, including PAR levels in tumor samples and gamma-H2AX levels in
peripheral blood mononuclear cells and tumor samples before and after treatment on protocol.
(Phase I and II) IV. To assess progression-free survival, overall survival, and duration of
remission of patients with indolent NHL and MCL treated with ABT-888, bendamustine, and
rituximab. (Phase II)
OUTLINE: This is a dose-escalation, phase I study of veliparib followed by an expansion
cohort and phase II study.
Patients receive veliparib orally twice daily on days 1-7 and bendamustine hydrochloride IV
over 30-60 minutes on days 1-2. Treatment repeats every 28 days for up to 6 courses in the
absence of disease progression or unacceptable toxicity.
Once the maximum-tolerated dose is determined, a cohort of patients receives veliparib and
bendamustine hydrochloride as above and rituximab IV on day 1. Treatment repeats every 28
days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and periodically during study for pharmacokinetic
and pharmacodynamic studies. Bone marrow biopsies and/or core tumor biopsies samples may
also be collected.
After completion of study therapy, patients are followed up for 30 days.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of veliparib in combination with bendamustine (phase I)
Toxicities will be graded and reported according to criteria listed in CTCAE ver. 4.0.
Up to 6 courses
Yes
John Gerecitano
Principal Investigator
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
NCI-2011-02583
NCT01326702
July 2011
Name | Location |
---|---|
Memorial Sloan Kettering Cancer Center | New York, New York 10021 |