Venetoclax with ivosidenib and azacitidine for newly diagnosed AML with an IDH1 mutation

A Multicenter, Single-Arm Clinical Study of the Venetoclax, Ivosidenib, and Azacitidine Triple-Drug Regimen in the Treatment of Chemotherapy-eligible Adult Patients With IDH1-Mutated Acute Myeloid Leukemia.

This treatment tests whether combining venetoclax, ivosidenib, and azacitidine helps people newly diagnosed with AML that has an IDH1 mutation.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 14 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT06611839 on ClinicalTrials.gov

What this trial studies

This phase 1/2 interventional study gives patients a combination of venetoclax (a BCL-2 inhibitor), ivosidenib (an IDH1 inhibitor), and azacitidine (a hypomethylating agent) to treat newly diagnosed IDH1-mutant AML. The rationale is that venetoclax plus hypomethylating agents has improved remission rates in older or unfit patients and ivosidenib targets the mutant IDH1 pathway that drives abnormal DNA methylation. The trial enrolls patients aged 14 and older with confirmed IDH1 mutations and good organ function and performance status (ECOG 0–2). All treatment and follow-up are conducted at the Blood Diseases Hospital in Tianjin, China, with dose-escalation and expansion components typical of phase 1/2 designs.

Who should consider this trial

Good fit: Ideal candidates are patients age 14 or older with newly diagnosed AML carrying an IDH1 mutation, ECOG performance status 0–2, and adequate liver, kidney, and cardiac function.

Not a fit: Patients without an IDH1 mutation, those with poor organ function or ECOG >2, or those unable to receive center-based care are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could increase remission rates and prolong survival for newly diagnosed IDH1-mutant AML patients, especially those who are unfit for intensive chemotherapy.

How similar studies have performed: Prior studies show venetoclax plus hypomethylating agents raised remission rates in older/unfit AML and ivosidenib is effective in IDH1-mutant AML, but combining all three agents is a relatively novel approach.

Eligibility criteria

Inclusion Criteria:

1. Patients who meet AML according to WHO (2022) or AML and MDS/AML defined by ICC standards with IDH1 mutations detected by PCR or second-generation sequencing.
2. Age ≥14 years old, male or female.
3. The physical status assessment (ECOG-PS) of the Eastern Oncology Collaboration group was 0-2 points.
4. Fulfill the requirements of the following laboratory tests (performed within 7 days prior to treatment) :

   1. Total bilirubin ≤ 1.5 times the upper limit of normal value (same age);
   2. AST and ALT≤ 2.5 times the upper limit of normal value (same age);
   3. Blood creatinine \< 2 times the upper limit of normal (same age);
   4. Myocardial enzymes \< 2 times the upper limit of normal (same age);
   5. Left ventricular ejection fraction \>50% by measure of echocardiogram (ECHO) Informed consent must be signed before the commencement of all specific study procedures, and is signed by the patient himself or his immediate family. Considering the patient\'s condition, if the patient\'s signature is not conducive to the treatment of the condition, the informed consent shall be signed by the legal guardian or the patient\'s immediate family.

Exclusion Criteria:

Subjects who meet any of the following criteria are excluded from the study:

1. Acute promyelocytic leukemia with PML-RARA fusion gene
2. Acute myeloid leukemia with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene
3. Acute myeloid leukemia with BCR-ABL fusion gene
4. Treated patients (but can receive hydroxyurea or cytarabine to lower tumor burden).
5. Concurrent malignant tumors of other organs (those requiring treatment).
6. Active heart disease, defined as one or more of the following:

   1. A history of uncontrolled or symptomatic angina;
   2. Myocardial infarction less than 6 months after enrollment;
   3. Have a history of arrhythmia requiring drug treatment or severe clinical symptoms;
   4. Uncontrolled or symptomatic congestive heart failure (\> NYHA level 2);
7. Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis).
8. Those who were not considered suitable for inclusion by the researchers.

Where this trial is running

Tianjin, Tianjin Municipality

• Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Hui Wei, MD — Blood diseases hospital
• Study coordinator: Hui Wei, MD

Conditions: AML, IDH1 Mutation, Treatment