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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MRX2843 orally 80 mg/d | Experimental | Participants received 80 mg MRX2843 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 21 of a 21-day cycle. |
|
| MRX2843 orally 120 mg/d | Experimental | Participants received 120 mg MRX2843 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 21 of a 21-day cycle. |
|
| MRX2843 orally 180 mg/d | Experimental | Participants received 180 mg MRX2843 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 21 of a 21-day cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MRX2843 | Drug | MRX2843 is treated at 80mg/d, 120mg/d and 180mg/d respectively |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety | Safety: Incidence of dose limiting toxicity (DLT)and Adverse Event (AE) | 28 Days |
| RP2D | Explore the maximum tolerated dose (MTD) and phase II recommended dose (RP2D), and initially formulate a reasonable dosing plan; | 28 Days |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum serum concentration (Cmax) | Maximum serum concentration (Cmax) | 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) |
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Inclusion Criteria:
Males and females age ≥ 18 years;
Expected survival period ≥ 12 weeks;
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
Histopathologically documented primary or secondary AML, as defined by WHO criteria, confirmed by pathology review at treating institution, meeting at least one of the following: i. After complete remission, leukemia cells reappear in peripheral blood, or the ratio of bone marrow immature cells to bone marrow cells> 5%, or leukemia cell infiltration outside the bone marrow; ii. After standard protocol (including cytarabine and a kind of Anthracycline or anthraquinone drugs) for refractory AML patients who have not achieved complete remission after two courses of treatment;
During the dose escalation phase, there is no need to test for FLT3 mutation status; for the expansion of the enrollment and phase II study phase, the FLT3 mutation status test results within the past 6 months will be accepted; if not, the central laboratory or research center needs to test and confirm the test Patients with FLT3 mutation status in bone marrow or whole blood. The test results show that the subject has any of the following FLT3 mutation types, and can be included in the group: FLT3 internal tandem repeat (ITD), FLT3 tyrosine kinase domain (TKD);
Laboratory inspection must meet the following standards:
Normal or abnormal ocular retinal examination has no clinical significance;
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Junmin Li, Ph.D | Contact | 13817712211 | Rjlijunmin@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Junmin Li,Ph.D | Shanghai | Shanghai Municipality | 200025 | China |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000726164 | MRX-2843 |
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| 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) | 28 Days |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 28 Days |
| Apparent volume of distribution at equilibrium after oral administration(Vss/F) | Apparent volume of distribution at equilibrium after oral administration(Vss/F) | 28 Days |
| Plasma Decay Half-Life (t1/2z) | Plasma Decay Half-Life (t1/2z) | 28 Days |
| Apparent Oral Clearance (CLz/F) | Apparent Oral Clearance (CLz/F) | 28 Days |
| Average plasma or serum concentration(Cav) | Average plasma or serum concentration(Cav) | 28 Days |
| changes in FLT3 mutation status in plasma | changes in FLT3 mutation status in plasma | 28 Days |
| Rate of Complete Remission (CR) | Rate of Complete Remission (CR) | 28 Days |
| Rate of partial remission (PR) | Rate of partial remission (PR) | 28 Days |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |