Actively Recruiting

Phase 1
Phase 2
Age: 14Years +
All Genders
NCT06611839

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

Led by Institute of Hematology & Blood Diseases Hospital, China · Updated on 2026-05-13

23

Participants Needed

1

Research Sites

154 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 14Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Diagnosis of AML according to WHO (2022) or ICC standards with IDH1 mutation confirmed by PCR or sequencing
  • Age 14 years or older
  • Male or female patients
  • Eastern Oncology Collaboration Group performance status (ECOG-PS) of 0 to 2
  • Laboratory tests within 7 days before treatment showing:
    • Total bilirubin less than or equal to 1.5 times the upper limit of normal for age
    • AST and ALT less than or equal to 2.5 times the upper limit of normal for age
    • Blood creatinine less than 2 times the upper limit of normal for age
    • Myocardial enzymes less than 2 times the upper limit of normal for age
    • Left ventricular ejection fraction greater than 50% measured by echocardiogram
  • Signed informed consent by the patient or legal guardian if the patient is unable to sign
Not Eligible

You will not qualify if you...

  • Acute promyelocytic leukemia with PML-RARA fusion gene
  • AML with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene
  • AML with BCR-ABL fusion gene
  • Patients who have received prior AML treatment (except hydroxyurea or cytarabine to reduce tumor burden)
  • Presence of other active malignant tumors requiring treatment
  • Active heart disease including:
    • Uncontrolled or symptomatic angina
    • Myocardial infarction within 6 months before enrollment
    • History of arrhythmia requiring drug treatment or with severe symptoms
    • Uncontrolled or symptomatic congestive heart failure (greater than NYHA level 2)
  • Serious infections such as untreated tuberculosis or pulmonary aspergillosis
  • Any condition deemed unsuitable for study participation by the researchers

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

Blood Diseases Hospital

Tianjin, Tianjin Municipality, China, 300020

Actively Recruiting

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Research Team

H

Hui Wei, MD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

OTHER

Number of Arms

1

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