This phase II trial studies how well giving olutasidenib with azacitidine, followed by olutasidenib maintenance, works in treating patients with IDH1-mutated acute myeloid leukemia (AML) who have received prior treatment with venetoclax plus a hypomethylating agent (HMA-Ven). Olutasidenib and azacitidine may inhibit the growth of cancer cells by blocking certain enzymes required for cell growth. Maintenance therapy can help prevent or delay cancer from coming back. Olutasidenib with azacitidine followed by olutasidenib maintenance may be effective in treating patients with IDH1-mutated AML who have received prior HMA-Ven.
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
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
Single group
Azacitidine
DrugGiven IV or SC
Olutasidenib
DrugGiven PO
Treatment failure
Defined as the percent of patients who reached death due to acute myeloid leukemia (AML), relapse, or discontinuation of treatment due to an adverse event, at 12 months from the time of CR/CRi in patients with AML who begin first line venetoclax plus a hypomethylating agent regimen and subsequently transition to olutasidenib maintenance. The Kaplan-Meier method will be employed to summarize the duration from the initiation of study treatment to treatment failure and to report the probability of being event-free at one year. The 1-year treatment failure rate will be reported along with its 95% confidence interval.
Median time to treatment failure
Will be reported along with its 95% confidence interval.
Incidence of adverse events (AEs)
All AEs will be listed, documenting the course, outcome, severity, and relationship to the study treatment. The proportion of participants experiencing AEs, serious adverse events, and treatment delays will be reported. Incidence rates of AEs and the proportion of participants prematurely withdrawn from the study due to AEs will be reported. AEs will be classified by severity and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Relapse free survival
Relapse categorized as CR, complete remission with partial hematologic recovery (CRh), or CRi, will be determined according to the European Leukemia Net (ELN) guidelines. Will be summarized using the Kaplan-Meier method. Will be reported along with its 95% confidence interval.
Duration of remission
Remission categorized as CR, CRh, or CRi, will be determined according to the ELN guidelines. Will be summarized using the Kaplan-Meier method. Will be reported along with its 95% confidence interval.
Overall survival
Will be summarized using the Kaplan-Meier method. Will be reported along with its 95% confidence interval.
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University of California, Davis
Lead sponsor
National Cancer Institute (NCI)
Collaborator
