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Acute Myeloid LeukemiaPhase 1NCT07411586

Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 And IDH1 Co-Mutated Acute Myeloid Leukemia

A Phase 1 study testing Ziftomenib and Olutasidenib in people with Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The goal of Phase 1 is to find the recommended dose of ziftomenib and olutasidenib in patients with relapsed/refractory AML that has a mutation in the NPM1 and IDH1 genes. The goal of Phase 1b is to learn if the recommended dose of ziftomenib and olutasidenib found in Phase 1 can help to control the disease. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Ziftomenib and Olutasidenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
28 May 2026to 14 Jan 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Age > 18 years
  • Diagnosis of relapsed or refractory AML (including biphenotypic or bilineage leukemia) as defined by ≥ 5% marrow blasts; patients with isolated extramedullary AML without marrow involvement are not eligible
  • AML disease must be characterized by IDH1 and NPM1 co-mutations as determined by local molecular testing (next generation sequencing, PCR)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status </=2
  • Adequate renal function with CrCl ≥30 ml/min to be calculated using Cockroft Gault formula
  • Adequate hepatic function (total bilirubin < 3.0x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT < 3x ULN unless considered due to leukemic involvement, in which case total bilirubin < 5x ULN or AST and/or ALT < 5x ULN will be considered eligible
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  • Baseline QTcF ≤ 480 msec
  • In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation of study therapy will be 14 days from last cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half- lives of the prior therapy whichever is shorter. Cytarabine (up to 2 gm/m2), leukapheresis, and oral hydroxyurea are permitted in patients with rapidly proliferative disease before the start of study therapy for clinical benefit as needed. Hydroxyurea can also be administered during cycles 1-2 of study therapy for cytoreduction as deemed necessary by the treating physician and after discussion with the PI. Concurrent intrathecal therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
  • Female patients of childbearing potential must agree to use a highly effective method of contraception as well as a double-barrier method (e.g., condom with spermicide) and refrain from egg donation from screening visit until 180 days following the last dose of study intervention. Male patients capable of having intercourse with females of childbearing potential and who have not had vasectomies must agree to abstain from heterosexual intercourse or use a double-barrier method of contraception and have their partner use a highly effective method of contraception from the screening visit until 90 days following the last dose of study intervention. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study intervention. Please refer to NIH Contraception Guidance (https://rsc.niaid.nih.gov/sites/default/files/trpguidancereproriskfinal.pdf) for additional recommendations.
  • Willing and able to provide informed consent

Who cannot join

  • Patients with t (15;17) karyotypic abnormality or acute promyelocytic leukemia (French American- British [FAB] class M3-AML).
  • Patients with any concurrent uncontrolled clinically significant medical condition including life- threatening severe infection, or psychiatric illness, which could place the patient at unacceptable risk of study treatment or be unable to consent or comply with protocol therapy. Patients with controlled infections are allowed. Other prior or concurrent malignancies will be considered after discussion with the PI.
  • Patients with active, uncontrolled, leukemia involvement of the CNS
  • Patients with grade II-IV active or extensive chronic graft-versus-host disease (cGHVD) status post stem cell transplant requiring topical therapy. Patients must have discontinued calcineurin inhibitors at least 2 weeks prior to the start of the study therapy.
  • Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
  • Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
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  • Subject has a white blood cell count > 20 x 10⁹/L. (Note: Hydroxyurea, leukapheresis, and cytarabine is permitted to meet this criterion- see above Inclusion criteria #8.)
  • Prior treatment with ziftomenib or olutasidenib
  • Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception. Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example, a condom in combination with a spermicide).
  • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drugs including medical, psychological, familial, social or geographical consideration
  • Receiving treatment with moderate or strong CYP3A inducer within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study drug (see Appendix A for examples).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The University of Texas M. D. Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

The goal of Phase 1 is to find the recommended dose of ziftomenib and olutasidenib in patients with relapsed/refractory AML that has a mutation in the NPM1 and IDH1 genes.

The goal of Phase 1b is to learn if the recommended dose of ziftomenib and olutasidenib found in Phase 1 can help to control the disease.

The safety and effects of this combination will also be studied in both parts.

Read the detailed description

Primary Objectives:

  • Phase 1: To determine the safety and tolerability and recommended phase 2 dose (RP2D)) of ziftomenib and olutasidenib in adult patients with R/R NPM1 and IDH1 co-mutated AML
  • Phase 1b: To determine the preliminary efficacy of combination treatment as reflected by the composite remission rate (CRc=CR+ CRi +CRh) of ziftomenib and olutasidenib in adult patients with R/R NPM1 and IDH1 co-mutated AML

Secondary Objectives:

  • To determine the overall response rate (ORR) including composite remission rate (CRc), partial remission (PR), and morphologic leukemia free state (MLFS) following therapy
  • To determine the duration of response (DOR), event-free survival (EFS), relapse-free survival (RFS), time to CRc, and overall survival (OS) following therapy
  • To determine the occurrence of minimal residual disease (MRD) negative response (CR/CRi) as assessed by multiparameter flow cytometry and NPM1m qPCR following therapy
  • To determine the time to achieve CR/CRi following initiation of therapy
  • To determine the rate of transfusion independence (TI) achieved by patients on therapy
  • To determine the proportion of patients that undergo allogeneic stem cell transplantation (alloSCT) following study therapy
  • To monitor longitudinal changes in IDH1m VAF in patients following treatment

Exploratory Objective:

  • To perform detailed bulk and single cell multi-omics (DNA sequencing, RNA sequencing, global gene expression profiles, DNA methylation profiles), and other potential prognostic marker assays on longitudinally collected samples over the course of therapy to explore potential predictors of anti-tumor activity and/or resistance to treatment
Being tested
Ziftomenib, Olutasidenib
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • ZiftomenibDrug

    Also called Komzifti

    Given by mouth

  • OlutasidenibDrug

    Also called Rezlidhia

    Given by mouth

Study groups in NCT07411586
Study groupRoleWhat they receive
Phase 1 Escalation and Phase 1b Expansion: Treatment with Ziftomenib + OlutasidenibExperimentalAdult participants with relapsed/refractory NPM1m/ IDH1m AML will be enrolled. Treatment will consist of 28-day cycles of ziftomenib and olutasidenib given concomitantly. All participants will receive olutasidenib 150 mg orally twice daily (total 300 mg dose per day).
Receives: Drug: Ziftomenib; Drug: Olutasidenib

What is being measured

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

  1. Safety and Adverse Events (AEs)

    Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

    Measured: Through study completion; an average of 1 year

Timeline

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

  1. First posted17 Feb 2026
  2. Study start28 May 2026
  3. Primary completion14 Jan 2027 (estimated)
  4. Study completion14 Jan 2029 (estimated)

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07411586
Sponsor's protocol ID
2025-1468
Other IDs
NCI-2026-01058
Status last verified
Aug 2026
First submitted
11 Feb 2026
Last updated
24 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ziftomenib and Olutasidenib in people with Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site 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 10 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

This study is still under way. Results are not available in the source record yet.

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?

Safety and Adverse Events (AEs) (time frame: Through study completion; an average of 1 year). 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 NCT07411586.

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 24 Aug 2026.

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