Overview
Pharmacokinetic and Safety Study of MRX-2843 in Adolescents and Adults With Relapsed/Refractory AML, ALL, or MPAL
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2024-01-31
2024-01-31
Target enrollment:
0
0
Participant gender:
All
All
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.Phase:
Phase 1Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Meryx, Inc.
Criteria
Inclusion Criteria:- 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:
1. Bilirubin ≤ 1.5 the upper limit of normal (ULN). For patients with documented
Gilbert's disease, bilirubin ≤ 3.0 mg/dL
2. 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)
3. 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.
Exclusion Criteria:
- To be eligible for this study, each of the following criteria must be satisfied with a
"NO" answer:
All Subjects:
- Patient has diagnosis of acute promyelocytic leukemia (or AML M3).
- Patients with known active CNS leukemia.
- Patient has any surgical or medical condition (active or chronic) that may interfere
with drug absorption, distribution, metabolism, or excretion of the study drug, or any
other condition that may place the patient at risk.
- Patient has a history of other malignancies that have required systemic treatment
within the last 2 years or are deemed by the investigator to have a potential to
interfere with the safety and efficacy assessment of MRX2843. Patients with treated
nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia,
regardless of the disease-free duration, are eligible for this study if definitive
treatment for the condition has been completed.
- Patient has received radionuclide treatment within 6 weeks of the first dose of study
treatment.
- Patient has received systemic antineoplastic therapy within 14 days of study treatment
or 6 weeks for nitrosoureas or mitomycin C. (However, hydroxyurea can be given for the
purposes of cytoreduction up to 1 day prior to enrollment, with the exceptions noted
above in the inclusion criteria).
- Patient has not fully recovered from acute toxic effects due to all prior therapies,
except alopecia and other non-clinically significant AEs prior to enrollment.
- Patient has active clinically significant GvHD.
- Patient has received calcineurin inhibitors within four weeks of study treatment.
- Patient is known to have human immunodeficiency virus infection (HIV).
- Patient has used a small molecular kinase inhibitor or any investigational drug or
product within 28 days or 5 half lives, whichever is longer, before study drug dosing.
- Patient has a diagnosis of active hepatitis B or C.
- Patient has an active uncontrolled infection.
- Patient has a history of Type 1 Diabetes (T1D) or is considered at high risk for T1D,
where high risk is defined as
1. Patient has 1 first-degree relative (FDR; defined as parents, offspring or
siblings) with T1D AND A1C value > 6.5% or
2. Patient has 2+FDR with T1D
- Patient has known or suspected history of retinitis pigmentosa or known or suspected
familial history of retinitis pigmentosa.
- Patient requires concomitant treatment, in therapeutic doses, with anticoagulants such
as warfarin or coumadin-related agents, thrombin or FXa inhibitors, and antiplatelet
agents (e.g., clopidogrel). Low dose aspirin (≤ 81 mg/day), low-dose warfarin (≤1
mg/day), and prophylactic Low Molecular Weight Heparin (LMWH) are permitted.
- Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4,
or patient with a history of congestive heart failure NYHA class 3 or 4 in the past,
unless a screening echocardiogram performed within 3 months prior to study entry
results in a left ventricular ejection fraction that is ≥ 45%.
- Patient has QTcF > 480 ms.
- Patient has had major surgery within 4 weeks of the first dose of study drug.
- The patient is unable or unwilling to abide by the study protocol or cooperate fully
with the investigator or designee.