Pharmacokinetic and Safety Study of MRX-2843 in Adolescents and Adults With Relapsed/Refractory AML, ALL, or MPAL
12 Years and older, Male and Female
2843-1003 (primary)
NCI-2021-13604
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.
Objectives
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.
Eligibility
- Patient is a male or female at least 12 years of age.
- Patient must weigh at least 40 Kg.
- Patient has histologically or cytologically confirmed diagnosis of AML as defined by the World Health Organization (WHO) criteria (2017), ALL, or MPAL and is in second or later relapse or is refractory to at least one induction regimen.
- The effects of MRX-2843 on developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to remain abstinent, or agree to practice double barrier forms of birth control in which 2 of the following precautions are used during the study and for 4 months after last dose of study drug(s): vasectomy, tubal ligation (or other transcervical sterilization procedures), vaginal diaphragm, intrauterine device, birth control pills, birth control implant, or condom or sponge with spermicide.
- Female patients of childbearing potential must be nonpregnant, nonlactating, and have a negative pregnancy test result at Screening and a negative pregnancy test on Day 1 of Cycles 1-4.
- Patient is able to provide written, informed consent or assent for patients < 18 years of age is provided along with parent/guardian consent before initiation of any study related procedures, and patient is able, in the opinion of the investigator, to comply with all the requirements of the study.
- Patient is able to swallow oral medication.
- Patient has white blood cell (WBC) lower than 25,000/mm3 at Screening prior to initiation of MRX-2843. Patients who are otherwise medically eligible for enrollment but have WBC above 25,000/mm3 are allowed concurrent treatment with hydroxyurea to stabilize the WBC. In these situations, hydroxyurea will be discontinued once WBC is below 10,000/mm3 and at least 1 day prior to start of study treatment. Treatment with hydroxyurea will be allowed during Cycle 1 if deemed needed by the Investigator.
- The Patient has laboratory values at Screening:
- Bilirubin = 1.5 the upper limit of normal (ULN). For patients with documented Gilbert's disease, bilirubin = 3.0 mg/dL
- Creatinine clearance (CrCl) = 60 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used: Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72) (For females: Multiply above result by 0.85)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3.0 × ULN
- Patient has Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or Lansky/Karnofsky = 50.
- For the FLT3ITD expansion cohort at RP2D, the FLT3ITD+ patients should have previously been treated with at least one FLT3 inhibitor prior to enrollment.
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
Click here to learn more about clinical trials.