Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia
University of Colorado, Denver
Summary
This is an open label, phase 1 study for AML subjects with relapsed or refractory disease or subjects in morphologic remission with MRD+ after first line therapy with venetoclax+HMA. A preliminary dose-finding cohort will be followed by 3 expansion cohorts.
Description
This is an open label, phase 1 study for AML subjects with relapsed or refractory disease or subjects in morphologic remission with MRD+ after first line therapy with venetoclax+HMA. A preliminary dose-finding cohort will be followed by 3 expansion cohorts. Cohort 1 will be a conventional 3+3 dose-escalation study to determine maximum tolerated (MTD) or recommended dose of mitoxantrone when used with venetoclax+azacitidine. Subjects who are refractory to first-line therapy with venetoclax+HMA, or who respond and then relapse after first line therapy with venetoclax+HMA, will enroll in the stu…
Eligibility
- Age range
- 18–80 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Subject must have confirmation of non-APL AML by WHO criteria and have been treated with first-line venetoclax/HMA (azacitidine or decitabine). 2. Subject must have relapsed disease per IWG criteria or disease refractory to first line venetoclax/HMA defined by less than a PR response after ≥ 1 complete cycle of venetoclax/HMA. 3. Subject must have either measurable residual disease (MRD+), as measured by FDA-approved flow cytometric test performed by Hematologics (cohort 3 and 4) or relapsed/refractory disease (cohort 1 and 2). 4. Subject must have an Eastern Cooperativ…
Interventions
- DrugVenetoclax
Venetoclax attaches to a protein called Bcl-2. This protein is present in high amounts in CLL cancer cells, where it helps the cells survive for longer in the body and makes them resistant to cancer medicines. By attaching to Bcl-2 and blocking its actions, venetoclax causes the death of cancer cells and thereby slows down progression of the disease.
- DrugAzacitidine
An analog of the pyrimidine nucleoside cytidine, has effects on cell differentiation, gene expression, and deoxyribonucleic acid (DNA) synthesis and metabolism, and causes cytotoxicity.
- DrugMitoxantrone
Mitoxantrone Injection, USP (concentrate) is a synthetic antineoplastic anthracenedione for intravenous use.
Location
- University of Colorado HospitalAurora, Colorado