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

NCT03564821 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 18-123
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

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)

Conditions

IDH1 Mutation Myeloid Neoplasms

Keywords

myeloid neoplasms

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Participants will be enrolled in standard 3 + 3 dose escalation cohorts in order to determine the maximum tolerated dose (MTD). The first 3 participants will be started on 500mg of Ivosidenib, administered daily for 28 consecutive days (1 cycle). If the 500mg/day dose level is tolerated, an additional 10 participants will be treated at this dose level. If the 500mg/day dose is not tolerated, the dose will be decreased to 250mg/day. If 250mg daily is tolerated, then an additional 10 participants will be treated at 250mg daily. The only doses studied will be 500mg daily and 250mg daily (the latter, if necessary). If 250mg daily dosing is not tolerated, then the study will end without expansion. Dose limiting toxicities are assessed and graded using Common Terminology Criteria for Adverse Events (CTCAE 4).

  28 Days

Secondary Outcomes (5)

• Ivosidenib-related Adverse Events, categorized by grade

  From the start of treatment until 30 days after the end of treatment, up to 13 months total

• Cumulative incidence of acute GVHD

  From the start of treatment with Ivosidenib until the onset of Acute GVHD, up to 100 days

• Cumulative incidence of chronic GVHD

  From the start of treatment with Ivosidenib until the onset of chronic GVHD, up to 24 months

• Plasma and marrow 2-hydroxyglutarate levels

  Screening, cycle 1 days 8 and 15 (cycles are 28 days), before the start of cycles 2 and 3, and at the time of relapse; up 24 months total time

• IDH clonal evolution and mutational burden

  Screening, cycle 1 days 8 and 15 (cycles are 28 days), before the start of cycles 2 and 3, and at the time of relapse; up 24 months total time

Study Arms (2)

Ivosidenib (500mg/day)

EXPERIMENTAL

-Ivosidenib will be administered orally every day

Drug: Ivosidenib

Ivosidenib (250mg/day)

EXPERIMENTAL

-Ivosidenib will be administered orally every day

Drug: Ivosidenib

Interventions

Ivosidenib DRUG

Ivosidenib is an inhibitor of the protein IDH1

Ivosidenib (250mg/day); Ivosidenib (500mg/day)

Eligibility Criteria

• Age: 18 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), 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:
• /6 or 6/6 (HLA-A, B, DR) matched related donor
• /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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Agios Pharmaceuticals, Inc.: collaborator

Study Sites (4)

Johns Hopkins Cancer Center

Baltimore, Maryland, 21218, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• 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.

  PMID: 33394722 DERIVED

MeSH Terms

Interventions

ivosidenib

Study Officials

• Amir T Fathi, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 7, 2018
• First Posted: June 21, 2018
• Study Start: January 16, 2019
• Primary Completion: May 22, 2022
• Study Completion: June 6, 2023
• Last Updated: November 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)