Olutasidenib With Azacitidine Followed by Olutasidenib Maintenance for the Treatment of IDH1-mutated Acute Myeloid Leukemia in Patients With Prior Treatment With Venetoclax Plus a Hypomethylating Agent

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Pathologically documented AML (except acute promyelocytic leukemia with the t(15;17) translocation) as defined by the World Health Organization (WHO) or International Consensus Classification criteria
• Achieved complete response (CR)/complete remission with incomplete count recovery (CRi) response to first line HMA-Ven according to the European Leukemia Net (ELN) recommendations for diagnosis as determined by investigator review
• Documented IDH1-R132 mutations (≥ 0.01%) detected in the bone marrow or blood. Mutation must be present at the time of AML diagnosis or after initiating HMA-Ven
• Receiving first-line HMA-Ven with less than or equal to 4 cycles of HMA-Ven at the time of enrollment. Participants must discontinue venetoclax (Ven) at least 1 week (or 5 half-lives, whichever is shorter) from initiating study treatment
• Candidate for standard of care azacitidine
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 50%)
• No prior solid organ allograft
• Recovery from the non-hematologic toxic effects of prior treatment to grade ≤ 1, or baseline value according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) classification (excluding infertility or alopecia)
• Aged ≥ 18 at the time of consent
• Creatinine clearance ≥ 40 mL/min (calculated by the Cockcroft-Gault formula or measured by 24-hour urine collection)
• Serum alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN)
• Serum aspartate aminotransferase (AST) ≤ 3 × ULN
• Bilirubin ≤ 2 x ULN unless due to Gilbert's syndrome or controlled autoimmune hemolytic anemia (not requiring immunosuppressive other than ≤ 20 mg of prednisolone daily)
• Note: Patients with Gilbert's syndrome may be included if total bilirubin is ≤ 3 × ULN and direct bilirubin is ≤ 2 × ULN
• Prothrombin time (PT) or international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
• Women of child-bearing potential, men, and their respective partners, must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days after the last dose of olutasidenib
• Must sign and date the informed consent form prior to undergoing any study procedures

You cannot join if

• Prior IDH1 inhibitor (IDH1i) targeted therapy
• Prior AML therapy except for HMA-Ven
• History of a different malignancy unless they have been disease-free for at least 12 months and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with a history of other malignancies within 12 months and without any evidence of disease progression or requiring therapy may be considered, but only after consideration and approval by the Overall Principal Investigator (PI). Individuals with the following cancers are eligible if diagnosed and/or treated within the past 12 months: cervical cancer in situ, breast ductal carcinoma in situ (DCIS), and basal cell or squamous cell carcinoma of the skin
• Patients with symptomatic central nervous system (CNS) metastases or other tumor location (such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention, palliative care, surgery or radiation therapy
• Patients with previous allogeneic hematopoietic stem cell transplantation (HSCT) for non-AML indications, if they meet any of the following criteria: < 100 days from time of HSCT; active acute or chronic graft versus (vs.) host disease (GvHD); or receiving immunosuppressive therapy as treatment or prophylaxis against GvHD
• Note: Doses < 20 mg methylprednisolone (or its equivalent) daily are not an exclusion criterion
• Treatment with radiation therapy or major surgery (requiring general anesthesia) within 2 weeks prior to study drug dosing
• Patients unable to swallow oral medications, or patients with gastrointestinal conditions (e.g., malabsorption, resection, etc.) deemed by the Investigator to jeopardize intestinal absorption
• Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris; previous history of myocardial infarction within one year prior to study entry, uncontrolled hypertension, or uncontrolled arrhythmias
• Patients with a baseline corrected QT interval by Fridericia's formula (QTcF) of > 480 msec
• Note: This criterion does not apply to patients with a bundle branch block (BBB); for participants with BBB, a cardiology consult is recommended to ensure that QTcF is not prolonged
• Concomitant medication(s) known to cause Torsades de Pointes (TdP) initiated less than the duration required to reach steady-state plasma concentration (approximately five half-lives) before first dose of study drug. Medications used as needed (PRN), e.g. Zofran, and common AML supportive care drugs (e.g. levofloxacin, azoles, etc.) are exempt
• Concurrent treatment with chronic corticosteroids except if chronic treatment with < 20 mg of methylprednisolone daily or equivalent (pulse steroids for treatment or prophylaxis are allowed [e.g., for transfusion or medication reactions])
• Known history of seropositivity for HIV infection
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy (prophylactic systemic antimicrobials permitted)
• Uncontrolled disease-related metabolic disorder (e.g., hypercalcemia)
• Pregnant, breastfeeding, or planning to become pregnant while enrolled in this trial or within 90 days after the last dose of olutasidenib. Pregnant or breastfeeding
• NOTE: Breast milk cannot be stored for future use while the mother is being treated on study)
• Plans to donate sperm or conceive a child through intercourse while enrolled in this trial or within 90 days after the last dose of olutasidenib
• Unwillingness or inability to comply with procedures either required in this protocol or considered standard of care
• Medical, uncontrolled disease-related metabolic disorder, psychiatric, cognitive, or other conditions that may, in the opinion of the investigator, compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol, or complete the study

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

olutasidenib. An orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1; IDH-1; IDH1 [NADP+] soluble) with a mutation at arginine (R) 132, IDH1(R132), with potential antineoplastic activity. Upon administration, olutasidenib specifically inhibits IDH1(R132), thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH(R132). IDH1(R132) mutations are highly expressed in certain malignancies, including gliomas; they initiate and drive cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG. NCI Drug Dictionary

azacitidine. A pyrimidine nucleoside analogue of cytidine with antineoplastic activity. Azacitidine is incorporated into DNA, where it reversibly inhibits DNA methyltransferase, thereby blocking DNA methylation. Hypomethylation of DNA by azacitidine may activate tumor suppressor genes silenced by hypermethylation, resulting in an antitumor effect. This agent is also incorporated into RNA, thereby disrupting normal RNA function and impairing tRNA cytosine-5-methyltransferase activity. NCI Drug Dictionary

Treatments listed in the registry

• Azacitidine (Drug): Given IV or SC
• Olutasidenib (Drug): Given PO

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• biopsy: Part of the study plan
• bone marrow: Part of the study plan
• blood samples: Part of the study plan

Main goals

• Treatment failure (At 12 months from complete response (CR)/complete remission with incomplete count recovery (CRi))
• Median time to treatment failure (From CR/CRi through death due to AML, relapse, or treatment discontinuation due to adverse event, assessed up to 4 years)

Other goals

• Incidence of adverse events (AEs)
• Relapse free survival
• Duration of remission
• Overall survival
• Rate of allogeneic hematopoietic cell transplants

Planned enrollment: 28 (estimated).

• UCI Health Chao Family Comprehensive Cancer Center, Orange, California
• University of California Davis Comprehensive Cancer Center, Sacramento, California

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07304011
• NCI Drug Dictionary: C129687
• NCI Drug Dictionary: C288

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 26, 2026. Public record; not medical advice.