CC-486 and Venetoclax for Acute Myeloid Leukemia
University of Colorado, Denver
Summary
This is an open label, dose escalation Phase I single institution pilot study for relapsed and refractory AML patients using CC-486 (oral azacitidine) with venetoclax. At the completion of dose escalation and after establishment of the MTD or recommended dose of CC-486 with venetoclax, an expansion phase will commence, using venetoclax with the MTD of CC-486 in relapsed/refractory patients.
Description
Subjects confirmed eligible will be admitted to the hospital for cycle 1, day 1. Venetoclax will be administered days 1-3, with the following schema: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3, and it will be continued at 400mg thereafter. Subjects taking concomitant CYP3A4 inhibitors will be given the appropriate reduced doses of venetoclax. Subjects will be monitored inpatient for tumor lysis syndrome (TLS) for at least 24 hours after administration of the venetoclax target dose. Venetoclax will continue at 400 mg daily until day 28, the completion of cycle 1. During dose escalati…
Eligibility
- Age range
- 18–100 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Subject must have confirmation of non-APL AML by WHO criteria46 and have undergone at least one line of therapy (dose escalation and dose expansion R/R cohorts), or have had no prior lines of therapy (newly diagnosed cohort) Prior treatment with hydroxyurea or ATRA is allowed in the newly diagnosed cohort. 2. For the newly diagnosed cohort, subjects must be unlikely to tolerate standard intensive chemotherapy due to age, performance status, or comorbidities based on at least one of the following criteria: a. age ≥75 years old OR b. age \< 75 years old with at least…
Interventions
- DrugVenetoclax
Venetoclax is a potent, selective and orally bioavailable small molecule inhibitor of BCL-2 that binds with \> 1,000-fold higher affinity to BCL-2 (Ki \< 0.010 nM) than other apoptotic pathway proteins BCL-XL (Ki = 48 nm) or MCL-1 (Ki \> 444 nM). Leukemia stem cells (LSCs) overexpress BCL-2, and BCL-2 overexpression has been associated with worse outcomes in AML.
- DrugCC-486
An oral formulation of azacitidine currently being developed for the treatment of hematological and solid malignancies.
Locations (2)
- CU Anschutz Medical CampusAurora, Colorado
- University of Colorado HospitalAurora, Colorado