Phase I Study to Evaluate Safety of Ruxolitinib in Combination With Azacitidine + Venetoclax in Patients With Relapsed/Refractory Acute Myeloid Leukemia
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. Giving ruxolitinib in combination with venetoclax and azacitidine may be safe, tolerable, and/or effective compare to ruxolitinib with venetoclax in treating patients with relapsed or refractory AML.
• 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
⁃ Patients with morphologically documented myelodysplastic syndrome (MDS) that has progressed on hypomethylating agent (HMA) therapy also will be considered if the patient is ineligible for induction with intensive chemotherapy (IC), defined for this study as meeting one or more of the following criteria:
• Severe cardiac disorder (e.g., congestive heart failure requiring treatment, left ventricular ejection fraction (LVEF) of ≤ 50%, or chronic stable angina)
∙ Severe pulmonary disorder, certified by the managing physician
∙ Creatinine clearance of \< 45 ml/min or
∙ Hepatic disorder with total bilirubin \> 1.5 x upper limit of normal (ULN)
∙ Eastern Cooperative Oncology Group (ECOG) equal to 2
∙ Other comorbidity(ies) judged to be incompatible with high dose chemotherapy by the managing physician will be considered, at the discretion of the principal investigator (PI)
• ECOG performance status 0 to 2
• Persons of childbearing potential (PCBP) must have a negative serum or urine pregnancy test within 14 days prior to start of study drug administration
• Patients must agree to use an adequate method of contraception while on study treatment and for 120 days after the last dose of ruxolitinib for Arm 1 and 6 months after the last dose of azacitidine for Arm 2
• Must be able to take and absorb oral medications
• Creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hour urine collection
• Total serum bilirubin ≤ 1.5 x ULN unless thought to be due to leukemic involvement
• Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3.0 x ULN unless thought to be due to leukemic involvement