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

Oncology

Journal of Leukemia

Author(s): Brown JR, Tesar B, Yu L, Werner L, Takebe N, Mikler E, Reynolds HM, Thompson C, Fisher DC, Fisher DC, Freedman AS

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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.

This article was published in Leuk Lymphoma and referenced in Journal of Leukemia

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