This phase II trial tests how well olutasidenib in combination with hypomethylation therapy (azacitidine, decitabine, and decitabine/cedazuridine) works in treating patients with IDH1-mutated higher risk myelodysplastic syndromes, chronic myelomonocytic leukemia, or myeloproliferative neoplasms. Olutasidenib inhibits the proliferation of tumor cells expressing mutated IDH1. Azacitidine inhibits certain enzymes, which can lead to the activation of tumor suppressor genes that help kill of cancer cells. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Azacitidine, decitabine, and decitabine/cedazuridine are approved for the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia, but not myeloproliferative neoplasms. Combining olutasidenib with hypomethylation therapy may be more effective at treating patients with IDH1-mutated myelodysplastic syndromes, chronic myelomonocytic leukemia, or myeloproliferative neoplasms than giving either alone.
Additional locations may be listed on ClinicalTrials.gov for NCT06597734.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: Kelly S. Chien
Phone: 713-745-7584
PRIMARY OBJECTIVE:
I. To determine the overall response rate of olutasidenib in combination with investigator’s choice of hypomethylating agent (HMA) in patients with IDH1-mutated higher-risk myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) or advanced myeloproliferative neoplasm (MPN).
SECONDARY OBJECTIVES:
I. To evaluate the rates of complete remission (CR) and median duration of CR.
II. To ascertain the safety and tolerability of olutasidenib with HMA in this patient population.
III. To determine survival including overall survival (OS), progression-free survival (PFS), and duration of response (DOR).
IV. To analyze reduction in IDH1 clone size.
EXPLORATORY OBJECTIVES:
I. To examine overall response rate of patients previously exposed to venetoclax.
II. To investigate global gene expression profiles, deoxyribonucleic acid (DNA) methylation profiles, and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment.
OUTLINE:
Patients receive olutasidenib orally (PO) twice daily (BID) on days 1-28 of each cycle. Patients also receive either azacitidine intravenously (IV) over 15 minutes or subcutaneously (SC) once daily (QD) on days 1-7 of each cycle, decitabine IV over 60 minutes on days 1-5 of each cycle, or decitabine and cedazuridine (decitabine/cedazuridine) PO QD on days 1-5 of each cycle, per the investigator's choice of HMA. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and/or biopsy and collection of blood samples throughout the study.
After completion of study treatment, patients are followed up every 3 months for up to 3 years.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorKelly S. Chien
