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IDH1 Mutation Myeloid NeoplasmsPhase 1NCT03564821

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

A Phase 1 study testing Ivosidenib in people with IDH1 Mutation Myeloid Neoplasms, run by Massachusetts General Hospital at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
IDH1 Mutation Myeloid Neoplasms
What is being tested?
Ivosidenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
4 sitesUnited States
Study dates
16 Jan 2019to 6 Jun 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Johns Hopkins Cancer Center

    Baltimore, Maryland, 21218

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Massachusetts General Hospital

    Boston, Massachusetts, 02214

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase 1 Study of IDH1 Inhibition Using Ivosidenib as Maintenance Therapy for IDH1-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation

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)

Read the 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.

Being tested
Ivosidenib
Keywords
myeloid neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IvosidenibDrug

    Ivosidenib is an inhibitor of the protein IDH1

Study groups in NCT03564821
Study groupRoleWhat they receive
Ivosidenib (500mg/day)Experimental-Ivosidenib will be administered orally every day
Receives: Drug: Ivosidenib
Ivosidenib (250mg/day)Experimental-Ivosidenib will be administered orally every day
Receives: Drug: Ivosidenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 28 Days

Secondary outcomes (5)

  1. Ivosidenib-related Adverse Events, categorized by grade

    Adverse events will be assessed and graded using Common Terminology Criteria for Adverse Events (CTCAE 4).

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

  2. Cumulative incidence of acute GVHD

    Cumulative incidence of acute graft versus host disease (GVHD), measured from start of treatment with Ivosidenib.

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

  3. Cumulative incidence of chronic GVHD

    The cumulative incidence of chronic GVHD, measured from start of treatment with Ivosidenib. Chronic GVHD will be assessed using the National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease.

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

  4. Plasma and marrow 2-hydroxyglutarate levels

    Measured: 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

  5. IDH clonal evolution and mutational burden

    Isocitrate dehydrogenase (IDH) clonal evolution and mutational burden in patients with IDH1-mutant myeloid neoplasms who receive Ivosidenib after hematopoietic stem cell transplantation. Next-generation sequencing will be used to assess mutational burden (i.e. the fraction of AML cells harboring IDH mutations, corrected for copy number) at various time points. SNaPshot genotyping analysis platform will be used to perform these analyses.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2018
  2. Study start16 Jan 2019
  3. Primary completion22 May 2022
  4. Study completion6 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03564821
Sponsor's protocol ID
18-123
Status last verified
Oct 2025
First submitted
7 Jun 2018
Last updated
4 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33394722

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ivosidenib in people with IDH1 Mutation Myeloid Neoplasms, run by Massachusetts General Hospital at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (time frame: 28 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03564821, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2025.

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