Venetoclax in Combination With Ivosidenib and Azacitidine for Newly Diagnosed IDH1-Mutated AML

Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Study ID
NCT06611839
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • AML
  • IDH1 Mutation
  • Treatment

Eligibility Criteria

Sex
ALL
Age
14 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Ivosidenib, Venetoclax, Azacitidine — DRUG
    Induction therapy：Ivosidenib 500mg d1-28 Venetoclax 100mg d1，200mg d2，400mg d3, 800mg d4-14 Azacitidine 75mg/m2/d, d1-7 . Consolidation therapy: intermediate-dose cytarabine regimen ： 3 courses If IDH1 mutant residual disease was positive before consolidation chemotherapy, Ivosidenib was added; Maintenance treatment: Azacitidine、Venetoclax 、Ivosidenib： 6 courses

Study Details

Venetoclax can bind to the BCL-2 protein, thereby initiating the apoptosis program and exerting anti-AML effects. The induction regimen combining venetoclax with hypomethylating agents (HMA) significantly improves the remission rate (over 60%) in elderly unfit AML patients and markedly prolongs survival in those achieving complete remission. Isocitrate dehydrogenase (IDH) 1 and 2 are involved in the citric acid cycle. Approximately 20% of AML patients carry IDH1 or IDH2 mutations, which lead to the reduction of α-ketoglutarate to 2-hydroxyglutarate (2-HG). 2-HG can cause histone methylation and inhibit TET2 activity, resulting in DNA hypermethylation, thereby affecting gene expression and cell differentiation. IDH mutations are more common in elderly patients and are often associated with cytogenetic abnormalities; they may also co-occur with FLT3-ITD, NPM1, or DNMT3A mutations. Ivosidenib is an IDH1 inhibitor, and previous studies have confirmed its safety and efficacy in AML treatment. According to adult AML treatment guidelines, IDH-mutated patients eligible for intensive chemotherapy may receive IDH inhibitors during induction therapy. Based on the study by Montesinos et al. on the role of ivosidenib and azacitidine in IDH-mutated AML, for patients ineligible for intensive chemotherapy, a new treatment option has been added: IDH1-mutated AML patients may receive ivosidenib (500 mg, days 1-28) combined with azacitidine (75 mg/m²/day for 7 days) in 28-day cycles, or ivosidenib monotherapy. Recent studies have shown that a triple-drug regimen comprising ivosidenib, venetoclax, and azacitidine demonstrates excellent efficacy and safety. In chemotherapy-ineligible patients, the triple regimen achieved a composite complete remission rate (CRc) of 86% and an overall response rate (ORR) of 92%. At a median follow-up of 27.4 months, the 2-year overall survival (OS) was 72%, and the 2-year event-free survival (EFS) was 72%. Therefore, this study aims to conduct a multicenter, single-arm clinical trial to preliminarily evaluate the long-term efficacy of this combination in adult AML.

Key Dates

Start date
Oct 17, 2025
Status verified
May 2026
Primary completion
Oct 1, 2026
Completion
Oct 1, 2028

Study Design

Enrollment
23 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER

Arms

  • Experimental: Venetoclax、Ivosidenib and Azacitidine
    Induction regimen includes venetoclax, ivosidenib and azacitidine followed by consolidation therapy with intermediate dose of cytarabine.

Primary Outcome Measure

CRc rate [ Time Frame: Efficacy was assessed at least 2 weeks after completion of the first course of induction therapy. ]

Central Contacts

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