IDH1 Inhibition Using Ivosidenib as Maintenance Therapy for IDH1-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation

NCT ID: NCT03564821

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-16
• Study Completion Date: 2023-06-06

Brief Summary

This research study is studying a drug as a possible treatment for IDH1-mutant myeloid neoplasms.

-The drug involved in this study is ivosidenib (AG-120)

Detailed Description

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved ivosidenib as a treatment for any disease.

Ivosidenib is an inhibitor of the protein IDH1. Ivosidenib is currently being studied as a treatment for myeloid cancers like acute myeloid leukemia or myelodysplastic syndromes with an IDH1 mutation. This study is examining whether or not ivosidenib is beneficial and well-tolerated as an agent to prevent the relapse of IDH1-mutated acute myeloid leukemia or other myeloid neoplasms after hematopoietic stem cell transplantation. IDH1 is an enzyme that, when mutated, can overproduce metabolites (substances that help with metabolism) and compounds that contribute to the growth of tumors and cancerous cells. Ivosidenib may help block the over production of these substances and possibly reduce the chances of relapse.

Conditions

IDH1 Mutation Myeloid Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ivosidenib (500mg/day)

-Ivosidenib will be administered orally every day

Group Type: EXPERIMENTAL

Ivosidenib

Intervention Type: DRUG

Ivosidenib is an inhibitor of the protein IDH1

Ivosidenib (250mg/day)

-Ivosidenib will be administered orally every day

Group Type: EXPERIMENTAL

Ivosidenib

Intervention Type: DRUG

Ivosidenib is an inhibitor of the protein IDH1

Interventions

Ivosidenib

Ivosidenib is an inhibitor of the protein IDH1

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Pathologically confirmed diagnosis of IDH1(R132)-mutant acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML). 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).
• HSCT Donor will be one of the following:

• 5/6 or 6/6 (HLA-A, B, DR) matched related donor
• 7/8 or 8/8 (HLA-A, B, DR, C) matched unrelated donor. Matching in the unrelated setting must be at the allele level.
• Haploidentical related donor, defined as ≥ 3/6 (HLA-A, B, DR) matched --≥ 4/6 (HLA-A, B, DR) umbilical cord blood (UCB). Matching in the UCB setting is at the antigen level. Recipients may receive either one or two UCB units. In the case of 2 UCB units, both units must have been at least 4/6 matched with the recipient.
• 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

Exclusion Criteria

• Prior allogeneic hematopoietic stem cell transplants.
• Evidence of relapsed/recurrent/residual 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
• Systemic infection requiring IV antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection
• Uncontrolled intercurrent illness that would limit compliance with study requirements.
• HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with study drug. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agios Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Amir Fathi

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amir T Fathi, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Johns Hopkins Cancer Center

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Countries

United States

References

Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.

Reference Type: DERIVED

PMID: 33394722 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

18-123

Identifier Type: -

Identifier Source: org_study_id