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".
Age ≥18 years at time of signing the informed consent form.
Diagnosis of AML per the 2022 WHO Classification of Hematolymphoid Tumors (5th Edition).
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Adequate liver and kidney function according to protocol requirements.
Prior therapy for AML (except hydroxyurea or leukapheresis for WBC control).
Diagnosis of acute promyelocytic leukemia (APL), blast phase chronic myeloid leukemia, or isolated myeloid sarcoma.
Known history of BCR-ABL mutation.
Basal cell skin cancer or localized squamous cell cancer of the skin
Parallel
Ziftomenib
DrugOral administration
Placebo
DrugOral administration
Venetoclax
DrugOral administration
Azacitidine (AZA)
DrugIntravenous or subcutaneous administration
Daunorubicin
DrugIntravenous administration
Cytarabine (Ara-C)
DrugIntravenous administration
Nonintensive Therapy Study: (Primary Endpoint for all countries): Overall survival (OS)
OS
Nonintensive Therapy Study: (Dual Primary Endpoint for US & US reference countries only): Complete remission (CR)
CR rate per European Leukemia Network (ELN) 2022 criteria per Investigator assessment
Intensive Therapy Study: (Primary Endpoint for all countries): Event-free survival (EFS)
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
CR rate per ELN 2022 criteria per Investigator assessment with central BM MRD negativity
Nonintensive Therapy Study: (EU & EU reference countries only): Complete remission (CR)
CR rate per ELN 2022 criteria per Investigator assessment
Nonintensive Therapy Study: Bone marrow (BM) measurable residual disease (MRD) negativity
Central BM MRD negativity rate
Nonintensive Therapy Study: Complete remission (CR) + complete remission with partial hematologic recovery (CRh)
CR + CRh rate per ELN 2022 criteria per Investigator assessment
Nonintensive Therapy Study: Descriptive statistics of Adverse Events (AEs)
Assessed by NCI-CTCAE v5.0
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