Alvocidib is a potential new treatment for patients with acute myeloid leukemia (AML) that is currently being developed by Tolero Pharmaceuticals.

The U.S. Food and Drug Administration previously granted alvocidib orphan drug designation for the treatment of patients with AML.

How does alvocidib work?

Alvocidib is a potent inhibitor of a protein called cyclin-dependent kinase 9 (CDK9).

CDK9 promotes the production of a protein called MCL-1, which helps cancer cells survive by inhibiting apoptosis, or programmed cell death.

By blocking production of MCL-1, Alvocidib may promote the killing of cancer cells.

Alvocidib in clinical trials

A multicenter, open-label randomized Phase 2 clinical trial (NCT01349972) evaluated the efficacy of alvocidib in combination with cytarabine and mitoxantrone compared with the standard-of-care cytarabine and daunorubicin regimen in newly diagnosed, intermediate- and high-risk AML patients. Results from the study showed that the alvocidib, cytarabine, and mitoxantrone combination led to a more significant cancer reduction.

Another open-label, randomized Phase 2 trial (NCT02520011), called Zella 201, is recruiting about 79 patients with relapsed or refractory MCL-1 dependent AML, in the U.S., Canada, Spain, and the U.K. It is evaluating the combination of alvocidib, cytarabine, and mitoxantrone compared with cytarabine and mitoxantrone only. The study is expected to be completed in December 2020.

Alvocidib will also be evaluated in an open-label, randomized Phase 2 trial (NCT03969420), called Zella 202, which is recruiting up to 128 AML patients who have either relapsed from or are refractory to venetoclax in combination with a hypomethylating agent (azacitidine or decitabine). The two-part study will evaluate the safety and efficacy of alvocidib as a monotherapy or in combination with low-dose cytarabine. It is expected to be completed in September 2023.

An open-label Phase 1 trial (NCT03298984), called Zella 101, is recruiting about 25 patients with newly diagnosed AML in the U.S. to evaluate the safety, tolerability, and clinical activity of alvocidib in combination with cytarabine and daunorubicin.

An open-label Phase 1b trial (NCT03441555) is enrolling about 44 patients with relapsed or refractory AML in the U.S., Germany, and the U.K., to evaluate alvocidib in combination with venetoclax. The study is expected to be completed in September 2021.


Last updated: Jan. 27, 2020


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