An Open Label Evaluation Phase 1 Trial of the Safety and Pharmacokinetics of MRX-2843 in Adolescents and Adults With Relapsed/Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Mixed Phenotype Acute Leukemia
Summary
This is a Phase I, open-label, non-randomized, dose escalation study in adolescents and adults with relapsed/refractory acute myeloid leukemia, acute lymphoblastic leukemia, or mixed phenotype acute leukemia. Patients will receive continuous oral MRX-2843 in 28 day cycles at predefined dose cohorts.
Detailed description
This is a Phase I, open-label, non-randomized, dose escalation study in up to 50 adolescent or adult patients with relapsed/refractory acute myeloid leukemia, acute lymphoblastic leukemia, or mixed phenotype acute leukemia. Patients will receive a single dose of MRX-2843 followed by continuous oral MRX-2843 in 28 day cycles at predefined dose cohorts. A dose expansion arm of approximately 12 patients (with 6 patients being FLT3 ITD+ and 6 patients being Mer+/FLT3 WT) will be accrued to further evaluate patients at the RP2D.
Arms & interventions
- DrugMRX-2843
MRX-2843 capsules
Outcome measures
Primary
Percentage of subjects with Dose Limiting Toxicities (DLTs)
Time frame: Baseline to the end of Cycle 1 (up to 28 days)
Percentage of subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5
Time frame: Baseline up to 14 days after last dose of study treatment (up to approximately 8 months)
Secondary
Determine Maximum Tolerated Dose (MTD) in mg of MRX-2843
Time frame: Baseline to end of Cycle 1 (up to 28 days)
AUC0-t: area under the concentration-time curve from time 0 to the time of the last
Time frame: Day 1 and Day 23 of Cycle 1 (each cycle is 28 days)
AUC0-inf: area under the concentration-time curve from time 0 to infinity
Time frame: Day 1 and Day 23 of Cycle 1 (each cycle is 28 days)
AUC0-τ: area under the concentration-time curve from time 0 to tau, where tau is the dosing interval
Time frame: Day 1 and Day 23 of Cycle 1 (each cycle is 28 days)
Cmax: maximum observed plasma concentration
Time frame: Day 1 and Day 23 of Cycle 1 (each cycle is 28 days)
Tmax: time to reach maximum observed plasma concentration
Time frame: Day 1 and Day 23 of Cycle 1 (each cycle is 28 days)
λz: terminal phase elimination rate constant
Time frame: Day 1 and Day 23 of Cycle 1 (each cycle is 28 days)
t1/2: apparent terminal elimination half-life
Time frame: Day 1 and Day 23 of Cycle 1 (each cycle is 28 days)
CL/F: apparent total body clearance
Time frame: Day 1 and Day 23 of Cycle 1 (each cycle is 28 days)
Vz/F: apparent volume of distribution of the terminal phase
Time frame: Day 1 and Day 23 of Cycle 1 (each cycle is 28 days)
Eligibility criteria
Study locations (3)
Emory University - WINSHIP Cancer Center
Atlanta, Georgia, 30322
Emory University, Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Memorial Sloan Kettering Cancer Center
New York, New York, 10065