Ziftomenib for the Treatment of Patients With NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia Not Eligible for Standard Therapy
NCT ID: NCT06930352
Last Updated: 2025-10-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE2
70 participants
INTERVENTIONAL
2026-01-10
2027-12-31
Brief Summary
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Detailed Description
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I. 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:
I. 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.
V. 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:
I. 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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (ziftomenib)
Patients 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.
Biospecimen Collection
Undergo blood sample collection
Bone Marrow Aspiration
Undergo bone marrow biopsy and/or aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy and/or aspiration
Cytarabine
Given cytarabine
Echocardiography Test
Undergo ECHO
Hydroxyurea
Given hydroxyurea
Leukapheresis
Undergo leukapheresis
Multigated Acquisition Scan
Undergo MUGA
Questionnaire Administration
Ancillary studies
Ziftomenib
Given PO
Interventions
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Biospecimen Collection
Undergo blood sample collection
Bone Marrow Aspiration
Undergo bone marrow biopsy and/or aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy and/or aspiration
Cytarabine
Given cytarabine
Echocardiography Test
Undergo ECHO
Hydroxyurea
Given hydroxyurea
Leukapheresis
Undergo leukapheresis
Multigated Acquisition Scan
Undergo MUGA
Questionnaire Administration
Ancillary studies
Ziftomenib
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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;
* 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
Exclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Kura Oncology
UNKNOWN
Uma Borate
OTHER
Responsible Party
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Uma Borate
Principal Investigator
Principal Investigators
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Uma M Borate, MBBS, MD, MSc
Role: PRINCIPAL_INVESTIGATOR
Ohio State University Comprehensive Cancer Center
Locations
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Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Countries
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Central Contacts
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Facility Contacts
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Related Links
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The Jamesline
Other Identifiers
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NCI-2025-02414
Identifier Type: REGISTRY
Identifier Source: secondary_id
OSU-24309
Identifier Type: -
Identifier Source: org_study_id
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