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

Más betegség

• Known history of BCR-ABL mutation.
• History of other active concurrent malignancies prior to study entry except:
  • Basal cell skin cancer or localized squamous cell cancer of the skin
  • Previous malignancy confined and locally resected (or treated with other modalities) with curative intent
  • Prostate or breast cancer receiving adjuvant hormonal therapy.
• Known uncontrolled HIV infection or known active hepatitis B virus, hepatitis C virus infection, or other uncontrolled infection.
• Uncontrolled intercurrent illness including but not limited to, cardiac illness as defined in the protocol.

Laborértékek

• Prior therapy for AML (except hydroxyurea or leukapheresis for WBC control).
• Clinical signs/symptoms of leukostasis or white blood cells (WBC) >25×10\^9/L prior to start of ziftomenib/placebo. Note: Hydroxyurea and/or leukapheresis are permitted to meet this criterion.

Egyéb

• Diagnosis of acute promyelocytic leukemia (APL), blast phase chronic myeloid leukemia, or isolated myeloid sarcoma.
• Active central nervous system (CNS) involvement by AML.
• Women who are pregnant or lactating.

• The following criteria apply to both the Nonintensive Therapy Study and the Intensive Therapy Study unless otherwise noted:
• 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.
• A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male with a female partner of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention.
• NONINTENSIVE THERAPY STUDY ONLY (VEN+AZA):
  • Documented NPM1-m.
  • Patients considered ineligible for Intensive Therapy defined by the following:
  • i. Age ≥75, OR
  • ii. Age <75 with an ECOG performance status of 2 or cardiac, renal, or hepatic impairment per protocol criteria.
• INTENSIVE THERAPY STUDY ONLY (7+3):
  • Documented NPM1-m or KMT2A-r (KMT2A-r patients with a partial tandem duplication are not eligible).
  • Documented FLT3 wild-type or ITD ratio <0.05 OR ineligible to receive FLT3-targeted therapy (medically ineligible or mutation in which FLT3 inhibition is not SOC). Lack of access to an FLT3 inhibitor is not considered "ineligible" for FLT3-targeted therapy.
  • Ejection fraction of ≥50%.
  • Fit for Intensive Therapy per Investigator opinion.