A Study of MRX2843 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

NCT04946890 | Unknown Phase 1

• 1 other identifier: BTP-66M12
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia Leukemia

Keywords

MRX2843

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (11)

• 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)

  28 Days

• 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)

  28 Days

• Apparent volume of distribution at equilibrium after oral administration（Vss/F）

  28 Days

Study Arms (3)

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.

Drug: MRX2843

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.

Drug: MRX2843

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.

Drug: MRX2843

Interventions

MRX2843 DRUG

MRX2843 is treated at 80mg/d, 120mg/d and 180mg/d respectively

MRX2843 orally 120 mg/d; MRX2843 orally 180 mg/d; MRX2843 orally 80 mg/d

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Blood routine: Under normal circumstances, the white blood cell count (WBC) ≤20×109/L; or the patient's white blood cell count (WBC)\>20×109/L before using hydroxyurea or cytarabine, use for a period of time and stop the drug After 3 days, check the white blood cell count (WBC) ≤20×109/L;
• Blood coagulation function: the international standardized ratio of prothrombin time and partial thromboplastin time ≤ 1.5 times the upper limit of normal (ULN);
• Liver: If there is no clear liver metastasis, serum total bilirubin ≤1.5 ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ULN; if there is clear Gilbert syndrome (Unconjugated hyperbilirubinemia), total bilirubin ≤ 3.0 ULN;
• Kidney: Serum creatinine (Scr) ≤1.5×ULN, or creatinine clearance (Ccr) ≥50 mL/min (calculated according to Cockcroft-Gault formula);
• Normal or abnormal ocular retinal examination has no clinical significance;

You may not qualify if:

• Previously received medications targeting MerTK and/or FLT3
• Histologic diagnosis of acute promyelocytic leukemia;
• Have had other malignant tumors in the past 5 years ;
• Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher;
• The tumor involves the central nervous system and/or the testis;
• Active, uncontrolled infection;
• Radiation therapy within 4 weeks prior to study;
• Received systemic glucocorticoids within 14 days before the first dose ；
• Left ventricular ejection fraction ≤1 × ULN,or﹤50%. Clinically significant ECG QTc prolongation (Male: \>450ms, Female: \>470ms).Significant cardiac disease；
• Human immunodeficiency virus positivity;
• Active hepatitis B or C or other active liver disease;
• Women who are pregnant, lactating;
• Have a history or family history of known or suspected retinitis pigmentosa;
• Inability to swallow drugs orally, and conditions that seriously affect the absorption or pharmacokinetic parameters of the test drug;
• History of type 1 diabetes;

Sponsors & Collaborators

• Betta Pharmaceuticals Co., Ltd.: lead

Study Sites (1)

Junmin Li，Ph.D

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

MRX-2843

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Junmin Li, Ph.D

CONTACT

13817712211; Rjlijunmin@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: July 1, 2021
• Study Start: July 1, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: July 1, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)