Obatoclax in combination with fludarabine and rituximab is well-tolerated and shows promising clinical activity in relapsed chronic lymphocytic leukemia

Abstract

Obatoclax is a small molecule mimetic of the BH3 domain of BCL-2 family proteins. This phase 1 study combining obatoclax with FR was undertaken in chronic lymphocytic leukemia (CLL) patients relapsed after at least one prior therapy. Obatoclax was given as a 3-h infusion on days 1 and 3 and escalated through three dose levels, with standard dose FR days 1–5. Thirteen patients were enrolled, with a median of two prior therapies. One dose-limiting toxicity (DLT) of a 2-week treatment delay for persistent grade 2–3 neutropenia was observed at the highest obatoclax dose (20 mg/m²), but no maximum tolerated dose (MTD) was reached. The overall response rate (ORR) was 85%, with 15% complete responses (CRs) by NCI-96 criteria and 54% by IWCLL 2008 criteria. Median time to progression was 20 months. It is concluded that obatoclax can be safely administered to relapsed CLL patients in combination with FR and shows promising clinical activity.

Keywords::

• Chronic lymphocytic leukemia
• phase I–III trials
• obatoclax
• BCL-2
• fludarabine
• rituximab

Acknowledgements

We are indebted to the nurses and clinical research staff of the Dana-Farber Cancer Institute for their excellent care of these patients and to the patients for their participation in this study. JRB was supported by NIH grant K23 CA115682-01 and is a Scholar of the American Society of Hematology as well as a Scholar in Clinical Research of the Leukemia and Lymphoma Society.

Potential conflict of interest:

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