Ivosidenib as Post-HSCT Maintenance for AML

NCT06707493 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-641
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 2 study of the study drug, ivosidenib (a mutant IDH1 inhibitor), compared to placebo, given to patients with IDH1-mutant acute myeloid leukemia (AML) after hematopoietic stem cell transplantation (HCT).

Conditions

Acute Myeloid Leukemia (AML); IDH1 Mutation; Hematopoietic Stem Cell Transplant (HSCT)

Keywords

hematopoietic stem cell transplantation (HCT); IDH1-mutant acute myeloid leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• Relapse-Free Survival (RFS)

  Relapse-Free Survival is defined as the time from randomization following transplant to disease relapse or death due to any cause, whichever occurs first. Participants alive without relapse are censored at the date of last seen alive. The primary analysis will be performed using the Kaplan-Meier method with log-rank test.

  Time of randomization to 24 months post-randomization, death, or disease relapse whichever occurs first.

Secondary Outcomes (5)

• Overall Survival (OS)

  Up to 39 months (Day of HCT (Day -90 to Day -45) through 24 months of treatment period and 12 months of follow-up)

• Incidence of treatment related adverse events (TRAE)

  Up to 25 months (Day 1 of study drug treatment for up to 24 months of treatment plus 30 days post final dose)

• Cumulative incidence of acute and chronic Graft vs. Host Disease (GVHD)

  Up to 36 months (Start of study treatment for 24 months, plus 12 months of follow-up)

• Measurable Residual Risease (MRD)

  Pre-transplant screening (up to Day -132) through 12 months of study treatment period, for up to 16.5 months.

• Cumulative incidence rate of relapse of acute myeloid leukemia (AML)

  From stem cell transplant through 12 months treatment period or relapse, whichever is first., up to 15 months.

Study Arms (2)

Ivosidenib

EXPERIMENTAL

After screening and standard of care hematopoietic stem cell transplantation (HCT) and any standard treatment before and after the HSCT, Ivosidenib will be given orally (PO) once daily (QD) in 28-day continuous cycles. Ivosidenib is administered at a pre-determined dose with a goal of 500mg daily. Participants begin study treatment 45 to 90 days after HCT, and treatment will continue for up to 24 months. Study visits and assessments occur throughout study treatment and in follow-up. After the 24-month treatment period, participants are followed for up to 12 additional months.

Drug: Ivosidenib

Placebo

PLACEBO COMPARATOR

After screening and standard of care hematopoietic stem cell transplantation (HCT) and any standard treatment before and after the HSCT, Placebo will be given orally (PO) once daily (QD) in 28-day continuous cycles. Participants begin study treatment (placebo) 45 to 90 days after HCT, and treatment (placebo) will continue for up to 24 months. Study visits and assessments occur throughout study treatment period and in follow-up. After the 24-month treatment period, participants are followed for up to 12 additional months.

Drug: Placebo

Interventions

Placebo DRUG

Placebo tablets are taken orally.

Placebo

Ivosidenib DRUG

Ivosidenib tablets are supplied as 50 mg, 200 mg, and 250 mg strengths, to be taken orally.

Also known as: AG-120, S95031

Ivosidenib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed diagnosis of IDH1(R132)-mutant acute myeloid leukemia (AML). IDH1 mutations could have been detected by any mutational technique at any prior point including at diagnosis or remission.
• Between the ages of 18 and 75 years
• Will undergo allogeneic hematopoietic stem cell transplantation (HSCT) for their malignancy. Conditioning may be either conventional myeloablative (MAC) or reduced intensity conditioning (RIC). There will be no restrictions on type of graft source.
• ECOG performance status ≤ 2
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1000/µL without growth factor support (e.g. GCSF) in the previous 7 days.
• Platelet count ≥ 50,000/µL without transfusional support in the previous 7 days.
• AST (SGOT), ALT (SGPT) and Alkaline phosphatase \< 3x institutional upper limit of normal (ULN)
• Direct bilirubin \< 2.0 mg/dL
• Calculated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula)
• LVEF must be equal to or greater than 40%, as measured by MUGA scan or echocardiogram
• Female patients of childbearing potential must have a negative pregnancy test
• The effects of ivosidenib on the developing human fetus are unknown. For this reason female participants of child-bearing potential and male participants must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during the entire study treatment period and through 90 days after the last dose of treatment
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Prior allogeneic hematopoietic stem cell transplants.
• Morphologically relapsed or refractory disease, as assessed by bone marrow aspirate and biopsy performed within 42 days prior to study entry
• History of other malignancy(ies) unless
• the participant has been disease-free for at least 5 years and is deemed by the investigator to be at low risk of recurrence of that malignancy, or
• the only prior malignancy was cervical cancer in situ and/or basal cell or squamous cell carcinoma of the skin
• Known diagnosis of active hepatitis B or hepatitis C
• Current or history of congestive heart failure New York Heart Association (NHYA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF \< 40%, as measured by MUGA scan or echocardiogram)
• Current or history of ventricular or life-threatening arrhythmias or diagnosis of long-QT syndrome
• QTc interval (i.e., Friderica's correction \[QTcF\]) ≥ 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening
• Uncontrolled intercurrent illness that would limit compliance with study requirements.
• Post-transplantation Pre-Treatment Criteria Treatment may begin at any time between day 45 and day 90 following stem cell transplantation.
• However, at time of treatment start, it must be ensured that:
• The patient has continued willingness and interest in participating in the study.
• There is no systemic infection requiring IV antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection
• Chimerism studies reveal that ≥ 70% of blood or bone marrow cells, or of the CD33 expressing fraction, are of donor origin,

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Servier: collaborator

Study Sites (4)

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ivosidenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Amir T Fathi, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amir T Fathi, MD

CONTACT

617-724-1124; afathi@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 23, 2024
• First Posted: November 27, 2024
• Study Start: January 16, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (4)