Milademetan Plus Quizartinib Combination Study in FLT3-ITD Mutant Acute Myeloid Leukemia (AML)
Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Relapsed/Refractory, Newly Diagnosed, Unfit for Chemotherapy, Positive for FLT3-ITD Mutation
Eligibility Criteria
Inclusion Criteria:
- Has reached ≥18 years old or the age of the age of majority in their country
- Part 1 (dose escalation): Has FLT3-ITD mutant (≥ 3% FLT3-ITD/total FLT3) AML (primary AML, secondary, or therapy-related AML), and has treatment failure to prior AML therapy or have relapsed after prior AML therapy
- Part 2 (dose expansion): Has FLT3-ITD mutant (≥3% FLT3-ITD/total FLT3) AML (primary, secondary, or therapy-related AML), and has treatment failure to prior AML therapy or have relapsed after prior AML therapy, OR has newly diagnosed AML who are ineligible for intensive induction chemotherapy
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (or 3 for patients with newly diagnosed AML between 18 and 74 years old)
- Has protocol-defined adequate renal, hepatic and cardiac status
- Is not pregnant, and if not postmenopausal or a surgically sterile male or female, is willing to use a highly effective contraceptive method upon enrollment, during the course of the study, and for 6 months following the last dose of investigational drug
- Is able and willing to provide protocol-defined bone marrow biopsies/aspirates
Exclusion Criteria:
- Has central nervous system (CNS) involvement of leukemia - patients with a history of CNS leukemia may be eligible if the CNS leukemia is adequately controlled (defined as no clinical symptoms of CNS disease and at least 2 consecutive lumbar punctures with no evidence of disease prior to study enrollment) after discussion and approval from the Sponsor
- Has acute promyelocytic leukemia (AML subtype M3)
- Has uncontrolled or significant cardiovascular disease or QTc interval >450 ms (average of triplicate determination)
- Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals.
- Has known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection based on positive tests during Screening
- Has persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapies
Has any history or medical condition, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
- safety or well-being of the participant or offspring
- safety of study staff
- analysis of results
Sites / Locations
- Ronald Reagan Medical Center, UCLA
- Yale Cancer Center
- University of Kansas Cancer Center
- Rogel Cancer Center, University of Michigan
- Roswell Park Comprehensive Cancer Center
- Duke University Cancer Center
- Sidney Kimmel Cancer Center, Thomas Jefferson University
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Part 1 - Quizartinib + Milademetan
Part 2 - Cohort 1
Part 2 - Cohort 2
Participants with relapsed/refractory FLT3-ITD Mutant AML receive quizartinib + milademetan at increasing and/or decreasing doses and schedules
Participants with relapsed/refractory FLT3-ITD Mutant AML receive the recommended dose of quizartinib + milademetan determined by Part 1
Participants with newly diagnosed FLT3-ITD Mutant AML unfit for chemotherapy receive the recommended dose of quizartinib + milademetan determined by Part 1