Ruxolitinib + Venetoclax

Undergo bone marrow aspiration and biopsy

PRIMARY OBJECTIVE: I. To evaluate an maximum-tolerated dose (MTD) for ruxolitinib in combination with Ia. Venetoclax (Arm 1); Ib. Venetoclax and azacitidine (Arm 2). SECONDARY OBJECTIVES: I. To assess the efficacy of the study treatment. II. To assess the duration of clinical response. III. To assess the duration of clinical benefit. IV. To assess survival in the absence of treatment failure, hematologic relapse, or progressive disease. V. To assess overall survival. VI.

To assess overall acute toxicity and tolerability. VII. To assess the effect of ruxolitinib in combination with azacitidine + venetoclax on quality of life (QOL). EXPLORATORY OBJECTIVES: I. To assess in vitro kinase inhibitor sensitivity using participants' bone marrow (or peripheral blood). II. To characterize changes in disease using molecular techniques (potentially including next-generation sequencing and/or BH3 profiling). III.

This phase I trial studies the side effects and best dose of ruxolitinib when given together with venetoclax and compares the effect of ruxolitinib in combination with venetoclax to venetoclax and azacitidine in treating patients with acute myeloid leukemia (AML) that has come back (relapsed) or has not responded to treatment (refractory). Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Azacitidine stops cells from making deoxyribonucleic acid and may kill cancer cells. It is a type of antimetabolite. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival.

Live record on ClinicalTrials.gov →

• Ability to understand and the willingness to sign a written informed consent document
• Age >= 18 years at time of informed consent. Persons of all genders and gender identities, and members of all races and ethnic groups will be included
• Morphologically documented relapsed/refractory (R/R) AML or R/R secondary AML (sAML) that has progressed after at least 1 prior therapy for AML
• Prior treatment with venetoclax and azacitidine is allowed
• Treatment with hydroxyurea will not be considered a line of therapy

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.