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

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.

Arms & interventions

• DrugZiftomenib

  Oral administration

• DrugPlacebo

  Oral administration

• DrugVenetoclax

  Oral administration

• DrugAzacitidine (AZA)

  Intravenous or subcutaneous administration

• DrugDaunorubicin

  Intravenous administration

• DrugCytarabine (Ara-C)

  Intravenous administration

Outcome measures

Eligibility criteria