Ivosidenib and Venetoclax With or Without Azacitidine in Treating Patients With IDH1 Mutated Hematologic Malignancies
Trial Parameters
Brief Summary
This phase Ib/II trial studies the side effects and best dose of venetoclax and how well it works when given together with ivosidenib with or without azacitidine, in treating patients with IDH1-mutated hematologic malignancies. Venetoclax and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ivosidenib and venetoclax with azacitidine may work better in treating patients with hematologic malignancies compared to ivosidenib and venetoclax alone.
Eligibility Criteria
Inclusion Criteria: 1. Age \> 18 years. 2. ECOG performance status of \< 2. 3. IDH1-R132 mutated disease status as assessed by local laboratory. 2HG-producing IDH1 variants outside of R132 (i.e. R100) may be eligible after discussion with the PI. 4. Relapsed/refractory AML, or treatment-naïve patients with AML who are not eligible for standard induction chemotherapy. Patients with high-risk MDS, MDS/MPN or MPN (defined as \> 10% bone marrow blasts, or intermediate or high risk by IPSS, R-IPSS or D-IPSS) that have failed standard therapy may also be eligible after discussion with the PI. 5. Adequate hepatic function (direct bilirubin \< 2 x ULN, ALT and/or AST \< 3x ULN) unless deemed to be related to underlying leukemia. 6. Adequate renal function including creatinine clearance \> 30 ml/min based on the Cockcroft-Gault equation. 7. Willing and able to provide informed consent 8. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation wil