NCT06930352

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

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

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: Uma Borate · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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. 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.

Detailed description

PRIMARY OBJECTIVE: 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

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow biopsy and/or aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy and/or aspiration
DRUG	Cytarabine	Given cytarabine
PROCEDURE	Echocardiography Test	Undergo ECHO
DRUG	Hydroxyurea	Given hydroxyurea
PROCEDURE	Leukapheresis	Undergo leukapheresis
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Ziftomenib	Given PO

Timeline

• Start date: 2026-04-10
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2025-04-16
• Last updated: 2026-03-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study