Obatoclax Mesylate, Rituximab, and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma
| Status: | Archived |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | October 2010 |
A Phase I/II Trial of Rituximab, Bendamustine, and Obatoclax in Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
RATIONALE: Obatoclax mesylate may stop the growth of cancer cells by blocking some of the
proteins needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer
growth in different ways. Some find cancer cells and help kill them or carry cancer-killing
substances to them. Others interfere with the ability of cancer cells to grow and spread.
Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways
to stop the growth of cancer cells, either by killing the cells or by stopping them from
dividing. Giving obatoclax mesylate together with rituximab and bendamustine hydrochloride
may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and the best dose of obatoclax
mesylate when given together with rituximab and bendamustine hydrochloride to see how well
it works compared with rituximab and bendamustine hydrochloride alone in treating patients
with relapsed or refractory non-Hodgkin lymphoma
OBJECTIVES:
Primary
- To determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of the
combination of obatoclax mesylate, rituximab, and bendamustine hydrochloride in
patients with relapsed or refractory, indolent, B-cell non-Hodgkin lymphoma (phase I).
- To define the qualitative and quantitative toxicities of the combination of obatoclax
mesylate, rituximab, and bendamustine (phase I).
- To detect an improvement in median progression-free survival (PFS) from 6 to 12 months
with the addition of obatoclax mesylate to rituximab and bendamustine hydrochloride in
patients with indolent B-cell non-Hodgkin lymphoma (phase II).
Secondary
- To determine the overall objective response rate to the combination of obatoclax
mesylate, rituximab, and bendamustine versus rituximab and bendamustine hydrochloride
in patients with relapsed or refractory, indolent, B-cell non-Hodgkin lymphoma.
- To characterize two-year PFS of patients with indolent B-cell non-Hodgkin lymphoma
receiving obatoclax mesylate, rituximab, and bendamustine hydrochloride versus
rituximab and bendamustine hydrochloride.
- To assess the pharmacokinetics of obatoclax mesylate in patients with relapsed or
refractory, indolent, B-cell non-Hodgkin lymphoma.
- To assess the pharmacokinetics of the combination of bendamustine hydrochloride and
obatoclax mesylate in patients with relapsed or refractory, indolent, B-cell
non-Hodgkin lymphoma.
- To determine the effects of the combination of rituximab, bendamustine hydrochloride,
and obatoclax mesylate on histone-oligodeoxynucleotide (ODNA) and levels of activated
Bax and Bak pro-apoptotic proteins in peripheral blood mononuclear cells and bone
marrow aspirate specimens.
- To identify associations of genetic polymorphisms in drug-metabolizing enzymes,
transporters, or target genes with pharmacokinetics, pharmacodynamics, or clinical
outcomes.
OUTLINE: This is a phase I, dose-escalation study of obatoclax mesylate followed by a
randomized phase II study.
- Phase I: Patients receive obatoclax mesylate IV over 3 hours on days 1-3, rituximab IV
over 4-8 hours on day 1 (day 3 of course 1), and bendamustine hydrochloride IV over 30
minutes on day 1-2 (day 2-3 of course 1). Treatment repeats every 28 days for a maximum
of 6 courses in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients are stratified according to prior bendamustine hydrochloride (yes vs
no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive obatoclax mesylate IV over 3 hours on days 1-3, rituximab
IV over 4-8 hours on day 1, and bendamustine hydrochloride IV over 30 minutes on
days 1-2.
- Arm II: Patients receive rituximab and bendamustine hydrochloride as in arm I. In
both arms, treatment repeats every 28 days for up to 6 courses in the absence of
disease progression or unacceptable toxicity.
Patients undergo blood and bone marrow sample collection at baseline and periodically during
study for pharmacokinetics, pharmacodynamic, and pharmacogenetic studies.
After completion of study therapy, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for phase I and a total of 70
patients will be accrued for phase II of this study.
We found this trial at
1
site
Columbus, Ohio 43210
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