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Phase 1 study of venetoclax/azacitidine or venetoclax in combination with ziftomenib (KO-539) or standard induction cytarabine/daunorubicin (7+3) chemotherapy in combination with ziftomenib for the treatment of patients with acute myeloid leukemia

Primary Investigator
Burke, Patrick
Status
OPEN TO ACCRUAL
Phase
I
NCT Number
NCT05735184
UM Number
2024.077
Age Group
Adults
Management Group
CTSU - Oncology
Oncology Group
Hematological Malignancies
ID (Protocol)
42015
Secondary Protocol No
HUM00252226
Scope
Unspecified
Sponsor Type
Industry
Disease Site
Myeloid and Monocytic Leukemia
Summary
This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3 for two different molecularly-defined arms, NPM1-m and KMT2A-r.

Eligibility: Inclusion Criteria
  •   Key
  •   * Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
  •   * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  •   * Adequate liver, renal, and cardiac function according to protocol defined criteria
  •   * 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 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
  •   Key
Exclusion Criteria
  •   * Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic leukemia
  •   * Known history of BCR-ABL alteration
  •   * Advanced malignant hepatic tumor [for patients receiving ven/aza combination]
  •   * Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery
  •   * Active central nervous system (CNS) involvement by AML.
  •   * Clinical signs/symptoms of leukostasis or WBC > 25,000 / microliter. Hydroxyurea and/or leukapheresis are permitted to meet this criterion
  •   * Not recovered to Grade =1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia
  •   * Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection
  •   * For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia, or non-HMA therapy for prior myelodysplastic syndrome
  •   * For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug
  •   * Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol
  •   * Mean corrected QT interval corrected for heart rate by Fredericia''s formula (QTcF) >480 ms on triplicate ECGs
  •   * Uncontrolled infection
  •   * Women who are pregnant or lactating
  •   * An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing