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

Condition(s) studied

Investigational drug(s) / intervention(s)

Ziftomenib: Oral administration

Placebo: Oral administration

Venetoclax: Oral administration

Azacitidine (AZA): Intravenous or subcutaneous administration

Daunorubicin: Intravenous administration

Cytarabine (Ara-C): Intravenous administration

Study 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".

Eligibility

Primary outcome measure(s)

• Nonintensive Therapy Study: (Primary Endpoint for all countries): Overall survival (OS) — Defined as the time from randomization to date of death from any cause, assessed up to 36 months after last patient inclusion
  OS
• Nonintensive Therapy Study: (Dual Primary Endpoint for US & US reference countries only): Complete remission (CR) — Assessed up to 36 months after last patient inclusion
  CR rate per European Leukemia Network (ELN) 2022 criteria per Investigator assessment
• Intensive Therapy Study: (Primary Endpoint for all countries): Event-free survival (EFS) — Defined as the time from randomization to treatment failure, hematologic relapse following CR, or death from any cause, whichever comes first, assessed up to 36 months after last patient inclusion
  EFS
• Intensive Therapy Study: (Dual Primary Endpoint for US & US reference countries only): Complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) negativity in NPM1-m patients — Assessed up to 36 months after last patient inclusion
  CR rate per ELN 2022 criteria per Investigator assessment with central BM MRD negativity

Trial sites (115)

+ 75 more sites — see the full list on the official registry below.