A Study of the Combination of Ivosidenib, Azacitidine, and Venetoclax Followed by Ivosidenib Alone in People With Acute Myeloid Leukemia

A Phase II Study of IDH1 Inhibition With Ivosidenib as Maintenance Therapy After Ivosidenib, Azacitidine, and Venetoclax for Acute Myeloid Leukemia

The researchers are doing this study to find out whether a 3-drug combination of ivosidenib, azacitidine, and venetoclax followed by maintenance therapy with ivosidenib alone is an effective treatment approach for people with newly diagnosed acute myeloid leukemia (AML) that has an IDH mutation. Maintenance therapy is additional treatment given to help keep cancer from coming back after it has disappeared following the first course of treatment. The researchers will also look at the safety of the treatment approach and what kind of a time commitment it involves for participants.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Ivosidenib; Drug: Azacitidine; Drug: Venetoclax

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eytan Stein, MD; Phone Number: 646-608-3749
• Study Contact Backup: Name: Kuo-Kai Chin, MD; Phone Number: 646-608-4415; Email: chin3@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memoral Sloan Kettering at Basking Ridge (Limited Protocol Activities)
      • Contact: Kuo-Kai Chin, MD; Phone Number: 646-608-4415
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Kuo-Kai Chin, MD; Phone Number: 646-608-4415
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Kuo-Kai Chin, MD; Phone Number: 646-608-4415
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk- Commack (Limited Protocol Activities)
      • Contact: Kuo-Kai Chin, MD; Phone Number: 646-608-4415
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited protocol activities)
      • Contact: Kuo-Kai Chin, MD; Phone Number: 646-608-4415
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All protocol activities)
      • Contact: Kuo-Kai Chin, MD; Phone Number: 646-608-4415
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activites)
      • Contact: Kuo-Kai Chin, MD; Phone Number: 646-608-4415

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be at least 60 years of age at the time of signing the informed consent form (ICF).
• Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
• Participant has newly diagnosed AML as per World Health Organization 2022 or European leukemia Network 2022 guidelines.

• Participant has IDH1-R132 mutation present prior to initiating Ivo/Aza/Ven confirmed by CLIA approved local testing via next-generation sequencing (NGS) and/or polymerase chain reaction (PCR). Other 2-HG producing IDH1 variants may be eligible after discussion with MSK principal investigator.

  1. At MSK, this testing will utilize the MSK-REACT, a rapid multi-gene NGS panel used in all new AML diagnoses that is clinically validated by the Laboratory of Diagnostic Molecular Pathology pursuant to the requirements of CLIA'88 and approved by New York State. Other sites may use local CLIA-certified laboratories and validated clinical assays as per standard of care.
  2. The patient's chart will be utilized for screening purposes
• Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
• Participant must have a WBC count <25,000/μL at the time of initiation of study drug (leukapheresis may be performed and/or hydroxyurea may be administered to decrease the WBC count to <25,000/μL).

• Participant has adequate organ function defined as:

  1. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x ULN, unless considered due to leukemic organ involvement.
  2. Serum total bilirubin < 3.0 x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis, leukemia organ involvement or Gilbert's syndrome.
  3. Serum creatinine < 2 x ULN or creatinine clearance 30 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation.

Exclusion Criteria:

• Participant with acute promyelocytic leukemia
• Participants who have previously received ivosidenib or venetoclax
• Participant receiving any other investigational anti-cancer agents. Cytoreductive therapy such as hydroxyurea is permitted.
• Participants with immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
• Participant has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).
• Participants who are planned for allogeneic stem cell transplantation based on the assessment of the treating clinician.
• Participant has significant active cardiac disease within 6 months prior to start of study treatment, including New York Heart Association (NYHA) class III or IV congestive heart failure; acute coronary syndrome (ACS); and/or stroke
• Participant has active viral infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). As per exclusion criteria 5, patients receiving appropriate treatment would only be excluded if there is no improvement.
• Participant is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
• Participant has QTc interval (i.e., Fridericia's correction [QTcF]) ≥ 450 ms (mean of triplicate ECG) or other factors that increase the risk of QT prolongation or ventricular arrhythmic events (e.g. family history of long QT interval syndrome). Participants with a QTcF over 450 ms due
• Male or female participants not willing to comply with contraceptive requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ivosidenib, Azacitidine, and Venetoclax Followed by Ivosidenib Alone; Patients will be initially treated with 7 days of azacitidine (IV or SC per institutional preference, 14 days of venetoclax and 14 days of Ivosidenib daily, days 15 through 28 for cycle 1, then days 1 through 28 for each cycle thereafter).	Drug: Ivosidenib; Ivosidenib ( days 15 through 28 for cycle 1, then days 1 through 28 for each cycle thereafter); Drug: Azacitidine; Azacitidine (IV or SC per institutional preference, days 1 through 7); Drug: Venetoclax; Venetoclax (days 1 through 14)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival	Event-free survival is defined as the time between date of treatment start to treatment failure (failure to achieve complete remission or <5% bone marrow blasts), confirmed relapse or death.	12 months

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Servier Pharmaceuticals, LLC
• Investigators: Principal Investigator: Kuo-Kai Chin, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: January 30, 2026
• First Posted (Actual): February 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Venetoclax; Azacitidine; Ivosidenib; 25-224
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax; ivosidenib
• Other Study ID Numbers: 25-224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No