Trial NCT05735184
A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML
- Phase
- Phase 1
- Sponsor
- Kura Oncology, Inc.
- Conditions
- Acute Myeloid Leukemia; Mixed Lineage Leukemia Gene Mutation; Refractory AML; AML With Mutated NPM1; Acute Myeloid Leukemia Recurrent; Acute Myeloid Leukemia, in Relapse; NPM1 Mutation; KMT2Ar; Myeloid Sarcoma; Nucleophosmin 1-mutated Acute Myeloid Leukemia
- Ages
- 18+ years
Eligibility criteria
Highlighted: restrictions our model extracted, each a verbatim quote (pink = excludes outright, blue = only under conditions).
Key Inclusion Criteria:
* Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
* Those intending treatment with intensive chemotherapy in Arm C should be NPM1-m and FLT3-ITD+ with an allelic ratio ≥0.05 and eligible for FLT3-targeted treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2Performance status
* Adequate liver, renal, and cardiac function according to protocol defined criteria
* A female of childbearing potential must agree to use adequate contraception as well as a double barrier method 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 use a double barrier method of contraception from the time of screening through 180 days following the last dose of study intervention
* Female patients of childbearing potential who receive quizartinib in Arm C should use a highly effective method of contraception during quizartinib treatment and for 7 months after the last dose
Key Exclusion Criteria:
* Diagnosis of either acute promyelocytic leukemia or blast phase chronic myeloid leukemia
* Known history of BCR-ABL alteration
* Advanced malignant hepatic tumor
* 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.Brain metastases
* Clinical signs/symptoms of leukostasis or WBC > 25,000 / microliter. Hydroxyurea and/or leukapheresis and/or up to 2 doses of cytarabine if used per institutional SOC for control of leukocytosis 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 infectionHIV
* For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis and/or up to 2 doses of cytarabine per institutional standards to control leukocytosis, or prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia
* 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 QT interval corrected for heart rate by Fredericia's formula (QTcF)Cardiac
* Arm A and Arm B: >480 ms on triplicate ECGs
* Arm C: >450 ms on triplicate ECGs
* Uncontrolled infection
* Women who are pregnant or lactatingPregnancy
* An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressingPrior malignancy
* Patients who have active GVHD requiring >0.5 mg/kg prednisone or any new or increase in immunosuppressants in the prior 2 weeks for GVHD treatment
Restrictions found (6)
- Brain metastasesConditionalexclusionShow in the text
- CardiacOutrightexclusion
QTcF >480 ms (Arm A and B); >450 ms (Arm C) on triplicate ECGs
Show in the text - HIVConditionalexclusionShow in the text
- Performance statusOutrightinclusion
ECOG 0, 1, or 2
Show in the text - PregnancyOutrightexclusionShow in the text
- Prior malignancyConditionalexclusionShow in the text
Recruiting in Massachusetts
- Massachusetts General Hospital · Boston, Suffolk County
- UMass Chan Medical School · Worcester, Worcester County