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:
To determine the safety and tolerability of ziftomenib combined with SOC treatments in adults
with newly diagnosed NPM1-m or KMT2A-r AML and for ziftomenib combined with SOC treatments
To determine the antileukemic activity of ziftomenib combined with SOC treatments in adults
with newly diagnosed NPM1-m or KMT2A-r AML and for ziftomenib combined with SOC treatments in NPM1-m or KMT2A-r patients with relapsed or refractory AML in NPM1-m or KMT2A-r patients with relapsed or refractory AML
Secondary:
To evaluate survival, disease control outcomes and additional markers of antileukemic activity for ziftomenib combined with SOC treatments in adults with newly diagnosed NPM1-m or KMT2A-r AML and for ziftomenib combined with SOC treatments in NPM1-m or KMT2A-r patients with relapsed or refractory AML
Characterize the pharmacokinetics of ziftomenib and metabolites when administered in combination with SOC treatments in adults with newly diagnosed NPM1-m or KMT2A-r AML and for ziftomenib combined with SOC treatments in NPM1-m or KMT2A-r patients with relapsed or refractory AML
To evaluate the potential drug interaction of ziftomenib on venetoclax (i.e., potential inhibition
of CYP3A4 metabolism of venetoclax by ziftomenib)
Venetoclax (ABT-199)
Ziftomenib
- Rutgers University
Key Inclusion Criteria: - 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
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.