Patients will receive oral MRX2843 for 28 days to study the side effects, tolerability and best dose for treating relapsed or refractory acute myeloid leukemia With FLT3 Mutations.
It is open-label, dose escalation study designed to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered MRX2843 as a single agent given daily for 28 days. The study includes two parts, Phase I and Phase II, and is carried out in three phases. The Phase I clinical study is divided into two phases: the dose escalation study (Ia) and the expanded enrollment study (Ib). The third phase is the phase II research phase, which is designed based on phase I clinical results. Phase Ia:Cohorts of 3 patients receive MRX2843 until dose limiting toxicity is noted (DLT). At that point cohorts will expand to 6 patients until MTD is determined. Phase Ib/ II:According to the relevant data on safety and effectiveness, expand the enrollment of FLT3 mutation relapsed/refractory AML patients at the appropriate dose
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
104
MRX2843 is treated at 80mg/d, 120mg/d and 180mg/d respectively
Junmin Li,Ph.D
Shanghai, Shanghai Municipality, China
Safety
Safety: Incidence of dose limiting toxicity (DLT)and Adverse Event (AE)
Time frame: 28 Days
RP2D
Explore the maximum tolerated dose (MTD) and phase II recommended dose (RP2D), and initially formulate a reasonable dosing plan;
Time frame: 28 Days
Maximum serum concentration (Cmax)
Maximum serum concentration (Cmax)
Time frame: 28 Days
Area under the plasma concentration-time curve (AUC) from time zero to the time point of t (AUC0-tn)
Area under the plasma concentration-time curve (AUC) from time zero to the time point of t (AUC0-tn)
Time frame: 28 Days
Area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC0-inf)
Area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC0-inf)
Time frame: 28 Days
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 28 Days
Apparent volume of distribution at equilibrium after oral administration(Vss/F)
Apparent volume of distribution at equilibrium after oral administration(Vss/F)
Time frame: 28 Days
Plasma Decay Half-Life (t1/2z)
Plasma Decay Half-Life (t1/2z)
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Time frame: 28 Days
Apparent Oral Clearance (CLz/F)
Apparent Oral Clearance (CLz/F)
Time frame: 28 Days
Average plasma or serum concentration(Cav)
Average plasma or serum concentration(Cav)
Time frame: 28 Days
changes in FLT3 mutation status in plasma
changes in FLT3 mutation status in plasma
Time frame: 28 Days
Rate of Complete Remission (CR)
Rate of Complete Remission (CR)
Time frame: 28 Days
Rate of partial remission (PR)
Rate of partial remission (PR)
Time frame: 28 Days