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Acute Myeloid LeukemiaPhase 2NCT06930352

Ziftomenib for the Treatment of Patients With NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia Not Eligible for Standard Therapy

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Acute Myeloid Leukemia, run by Uma Borate at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase II trial tests how well ziftomenib works in treating patients with NPM1 mutated or KMT2A rearranged acute myeloid leukemia (AML) and are not eligible to receive standard therapy. 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?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteUnited States
Study dates
1 Oct 2026to 31 Dec 2027
Phase
Phase 2
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

  • Signed informed consent must be obtained prior to participation in the study
  • Morphologically confirmed diagnosis of the following based on 2022 World Health Organization (WHO) Classification:
  • Treatment-naïve acute myeloid leukemia
  • KMT2A rearrangement (defined as KMT2A translocations) OR NPM1 mutation (defined as NPM1 mutation resulting in cytoplasmic localization, or NPM1c) OR other mutations that have been shown to exhibit sensitivity to menin inhibition. Mutation status will be known from initial diagnosis using standard of care testing, which can be performed locally
  • Patients ineligible or unwilling to receive standard of care induction therapy, such as 7+3, hypomethylating agent, venetoclax, or other standard of care (SOC) regimens with ineligibility defined by the following:
  • ≥ 75 years of age with both of the following;
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  • Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hours urine collection
  • Subject must have adequate liver function as demonstrated by aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (unless considered due to leukemic organ involvement) OR
  • ≥ 18 to 74 years of age with at least one of the following co-morbidities:
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3;
  • Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina;
  • Diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%;
  • Creatinine clearance ≥ 30 mL/min to < 45 ml/min;
  • Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 x ULN;
  • Venous thromboembolism benefitting from prolonged anticoagulation or presence of prosthetic heart valve or any indication for therapeutic anticoagulation with a single agent
  • Prior history of severe infection requiring hospitalization with risk of recurrence with subsequent immunosuppression
  • Any other comorbidity that the physician judges to be incompatible with standard frontline therapy must be reviewed and approved by the study team before study enrollment
  • Peripheral white blood cell (WBC) counts ≤ 10,000/uL. Patients may receive hydroxyurea, cytarabine, or leukapheresis to control and maintain white blood cell count until the end of cycle 1
  • Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 180 days after the last dose of study treatment
  • Non-sterile male patients must agree to use a highly effective method of contraception with partner(s) throughout the study and for at least 90 days after the last dose of study treatment

Who cannot join

  • Diagnosis of acute promyelocytic leukemia
  • Diagnosis of chronic myelogenous leukemia in blast crisis
  • Clinically active central nervous system (CNS) leukemia
  • Prior treatment for AML except for hydroxyurea and/or cytarabine used for control of leukocytosis
  • Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient
  • Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection. Patients with controlled disease will not be excluded from study enrollment
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  • Pre-existing disorder predisposing the patient to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML)
  • Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection
  • Mean Fridericia's formula-corrected QT interval (QTcF) > 480 ms on triplicate electrocardiogram (ECG)
  • Any psychiatric illness that prevents patient from informed consent process
  • Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to starting treatment
  • Participants requiring dual antiplatelet therapy

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ohio State University Comprehensive Cancer Center contact

800-293-5066

OSUCCCclinicaltrials@osumc.edu

United States1 site, 1 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Uma M. Borate, MBBS, MD, MSc, 614-685-9828, Uma.Borate@osumc.edu

    Uma M. Borate, MBBS, MD, MSc

    Recruiting

Other trials in United States

About this study

Official title: Frontline Ziftomenib in NPM1-Mutated or KMT2A-Rearranged Acute Myeloid Leukemia in Patients Not Eligible for Intensive Induction or Other Therapy

This phase II trial tests how well ziftomenib works in treating patients with NPM1 mutated or KMT2A rearranged acute myeloid leukemia (AML) and are not eligible to receive standard therapy. AML is often due to genetic changes in the cancer cells, including mutations in the NPM1 gene and rearrangements involving the KMT2A gene. These mutations result in activation of the menin pathway. Menin is a type of protein in the body that helps to regulate some of the naturally occurring processes in the body, but can also be involved in some types of cancers. Ziftomenib blocks this menin pathway and may prevent the cancer cells from continuing to grow. Giving ziftomenib may kill more cancer cells in patients with NPM1 mutated or KMT2A rearranged AML that are not eligible to receive standard therapy.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the efficacy of ziftomenib in treatment-naïve patients with KMT2A-rearranged (r) and NPM1-mutated (m) AML who are not candidates for standard therapy, with primary endpoint of complete remission (CR) + CR/response with hematologic improvement (CRh), assessed after 6 cycles of treatment using the best response achieved in that time.

SECONDARY OBJECTIVES:

  1. To determine rates of transfusion independence for 8- and 16-week periods. II. To determine response including CR, composite CR (CRc) (CR + CRh + CR with incomplete blood count recovery [CRi] + CR with incomplete platelet recovery [CRp]), proportion of patients achieving CRc with negative measurable residual disease (MRD), overall response rate (ORR) (CRc + partial response [PR] + morphologic leukemia free state [MLFS]).

III. To determine duration of response (DOR). IV. To determine overall survival (OS), and event free survival (EFS) at 24 months.

  1. To evaluate if ziftomenib treatment improves quality of life using the Patient Reported Outcomes Measurement Information System (PROMIS)-29+2 version (v) 2.1 questionnaire.

VI. To assess safety in this patient population by determining the number of patients experiencing adverse events/serious adverse events.

EXPLORATORY OBJECTIVES:

  1. To assess efficacy in patients with mutations thought to be sensitive to menin inhibition, other than KMT2A rearrangements and NPM1 mutations.

II. To perform measurable residual disease (MRD) monitoring via liquid biopsy to monitor clonal dynamics during treatment.

III. To assess the clonal, biochemical and differentiation changes in AML cells during treatment with menin inhibition using flow cytometry, cytogenetics and serial next generation sequencing on bone marrow specimens before and during treatment to assess for potential resistance mutations or clonal evolution that may be predictors of relapse.

OUTLINE:

Patients receive ziftomenib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo cytoreduction therapy with hydroxyurea up to end of cycle 1, cytarabine within 7 days of starting treatment, or leukapheresis within 7 days of treatment to reduce white blood cell count to =< 10,000/uL. Additionally, patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and bone marrow biopsy and/or aspiration and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 6 months for up to 24 months.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Cytarabine, Echocardiography Test
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.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and/or aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy and/or aspiration

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given cytarabine

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • HydroxyureaDrug

    Also called Droxia, Hydrea, Hydroxycarbamide, Litalir

    Given hydroxyurea

  • LeukapheresisProcedure or surgery

    Also called Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

    Undergo leukapheresis

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Questionnaire AdministrationOther

    Ancillary studies

  • ZiftomenibDrug

    Also called KO 539, KO-539, KO539, Menin-KMT2A Inhibitor KO 539

    Given PO

Study groups in NCT06930352
Study groupRoleWhat they receive
Treatment (ziftomenib)ExperimentalPatients receive ziftomenib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo cytoreduction therapy with hydroxyurea up to end of cycle 1, cytarabine within 7 days of starting treatment, or leukapheresis within 7 days of treatment to reduce white blood cell count to =< 10,000/uL. Additionally, patients undergo ECHO or MUGA at screening and bone marrow biopsy and/or aspiration and blood sample collection throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Procedure: Echocardiography Test; Drug: Hydroxyurea; Procedure: Leukapheresis; Procedure: Multigated Acquisition Scan; Other: Questionnaire Administration; Drug: Ziftomenib

What is being measured

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

  1. Complete remission (CR) plus CR/response with hematologic improvement

    Will be assessed after 6 cycles of treatment using the best response achieved in that time. Will be calculated in each arm for the efficacy analysis population and reported along with two-sided 95% exact binomial confidence limits, in a modified intent-to-treat analysis.

    Measured: After 6 cycles of treatment (cycle length = 28 days)

Secondary outcomes (10)

  1. Rate of transfusion independence

    Transfusion independence is defined as the proportion of subjects without transfusions during any consecutive 8 weeks (56 days) starting from Study Day 1 and has correlated with palliative benefits in patients with AML [19]. The major criteria for judging response will include physical examination and laboratory evaluation.

    Measured: Up to 24 months

  2. CR rate

    Will also be calculated in the primary efficacy analysis cohort along with 95% exact binomial confidence intervals.

    Measured: Up to 24 months

  3. Composite CR (CRc) rate

    Will also be calculated in the primary efficacy analysis cohort along with 95% exact binomial confidence intervals.

    Measured: Up to 24 months

  4. CRc with negative measurable residual disease

    Will also be calculated in the primary efficacy analysis cohort along with 95% exact binomial confidence intervals.

    Measured: Up to 24 months

  5. Overall response rate

    Will also be calculated in the primary efficacy analysis cohort along with 95% exact binomial confidence intervals.

    Measured: Up to 24 months

  6. Duration of response

    Will be estimated using the method of Kaplan-Meier and calculated in the primary efficacy analysis.

    Measured: From the date first achieved response to the date of progression or relapse or death, whichever occurs first, assessed up to 24 months

  7. Overall survival

    Will be estimated using the method of Kaplan-Meier and calculated in the primary efficacy analysis.

    Measured: From date of treatment start to death due to all causes, assessed up to 24 months

  8. Event free survival

    Will be estimated using the method of Kaplan-Meier and calculated in the primary efficacy analysis.

    Measured: From initiation of study treatment to the date of confirmed progressive disease, confirmed morphological relapse, treatment failure after 6 cycles of study treatment (cycle length = 28 days) or death from any cause, assessed up to 24 months

  9. Changes in quality of life

    Will be measured using Patient Reported Outcomes Measurement Information System (PROMIS) 29 +2 version (v) 2.1 and Patient Reported Outcomes (PRO) Common Terminology Criteria for Adverse Events (CTCAE). The raw sum will be calculated and converted to the standardized T score. Descriptive statistics will be used to present the PROMIS and PRO-CTCAE scores at each time point, and we will also use graphical display to visualize the change in quality of life over time. Wilcoxon signed rank test will be used to test if the change over time is statistically significant. To further quantify the change over time, linear mixed model will be fit for PROMIS score and PRO-CTCAE score, and if the sample size allows, the model will control for important clinical covariates as well.

    Measured: Day 1 of each cycle up to completion of treatment (cycle length = 28 days)

  10. Incidence of adverse events (AEs)

    AEs will be graded according to CTCAE v 5.0. The toxicity data captured will include type, frequency, grade, severity, timing of onset, duration, and relationship to study drug. Frequency tables will be used to summarize the AE data, where the number of patients with different types of AE will be tabulated by toxicity grade, counting only the highest grade of a certain type of AE occurred to the same patient. All adverse events regardless of attribution as well as those treatment-related AEs will be summarized.

    Measured: Up to 30 days after last dose of study treatment

Timeline

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

  1. First posted16 Apr 2025
  2. Study start1 Oct 2026 (estimated)
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06930352
Sponsor's protocol ID
OSU-24309
Other IDs
NCI-2025-02414
Status last verified
Aug 2026
First submitted
9 Apr 2025
Last updated
27 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 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Acute Myeloid Leukemia, run by Uma Borate 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 20 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: looking for participants now, as of the sponsor's last update on 27 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Contact Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCclinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete remission (CR) plus CR/response with hematologic improvement (time frame: After 6 cycles of treatment (cycle length = 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 NCT06930352.

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 27 Aug 2026.

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