NCT07007312

Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML

Phase 3 Randomized, Double-blind, Placebo-controlled Studies Assessing Ziftomenib in Combination With Either Standard of Care Nonintensive (Venetoclax+Azacitidine) or Intensive (7+3) Therapy in Patients With Untreated NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,300 (estimated)
• Sponsor: Kura Oncology, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with eligible genetic alterations. Ziftomenib is a type of therapy known to target the menin pathway in cancer cells. This protocol has 2 separate studies that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) AML treatments in patients with certain genetic mutations who have not received any treatment for their AML. In the first study, the Nonintensive Therapy Study, older patients or those with serious medical problems will receive the SOC therapies venetoclax (ven) and azacitidine (aza), plus either ziftomenib or a placebo. In the second study, the Intensive Therapy Study, medically fit patients will receive (a) the SOC therapies cytarabine and daunorubicin, plus either ziftomenib or a placebo during a first treatment phase called induction, (b) cytarabine plus either ziftomenib or a placebo during a second treatment phase called consolidation, and (c) ziftomenib or a placebo during a third treatment phase called maintenance. The physician will determine which study is the appropriate treatment for the patient, but neither the patient nor their physician will know whether the patient has been assigned to receive ziftomenib or a placebo. This design is called "double-blinded".

Detailed description

This protocol encompasses two phase 3, randomized, double-blind, placebo-controlled clinical studies to assess the efficacy, safety, and tolerability of ziftomenib in combination with: (a) the standard of care (SOC) nonintensive regimen (venetoclax \[ven\]+azacitidine \[aza\]) in untreated adults with nucleophosmin 1 mutated (NPM1-m) acute myeloid leukemia (AML); or (b) the SOC intensive regimen (cytarabine+daunorubicin induction, referred to here as 7+3, and cytarabine consolidation) in untreated adults with NPM1-m or lysine\[K\]-specific methyltransferase 2A rearranged (KMT2A-r) AML, as well as a maintenance phase. Nonintensive Therapy Study (Ven+Aza) Eligible NPM1-m patients will be enrolled and randomized to receive: * Arm A: Ziftomenib in combination with ven+aza or * Arm B: Placebo in combination with ven+aza. Patients will be randomized to treatment arms in a double-blind manner. Intensive Therapy Study (Cytarabine+Daunorubicin) Eligible NPM1-m or KMT2A-r patients will be enrolled and randomized to 1 of the following treatment arms: * Arm A: Ziftomenib+7+3 (induction), ziftomenib+cytarabine (consolidation), ziftomenib (maintenance) or * Arm B: Ziftomenib+7+3 (induction), ziftomenib+cytarabine (consolidation), placebo (maintenance) or * Arm C: Placebo+7+3 (induction), placebo+cytarabine (consolidation), placebo (maintenance). Patients will be randomized to treatment arms in a double-blind manner.

Conditions

• Acute Myeloid Leukemia (AML)

Interventions

Type	Name	Description
DRUG	Ziftomenib	Oral administration
DRUG	Placebo	Oral administration
DRUG	Venetoclax	Oral administration
DRUG	Azacitidine (AZA)	Intravenous or subcutaneous administration
DRUG	Daunorubicin	Intravenous administration
DRUG	Cytarabine (Ara-C)	Intravenous administration

Timeline

• Start date: 2025-09-26
• Primary completion: 2031-11-01
• Completion: 2031-11-01
• First posted: 2025-06-05
• Last updated: 2026-04-09

Locations

39 sites across 3 countries: United States, France, South Korea

Regulatory

• FDA-regulated drug study