Study of MAX-40279 in Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)

Study Overview
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Brief Summary
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This is a non-randomized, open-label, single-arm, dose-escalation Phase I study to evaluate the safety and tolerability of MAX-40279-01 in patients with Relapsed or Refractory AML.

Detailed Description
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This is a two-part study comprised of a dose escalation part and a dose expansion part.

Official Title
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A Phase I Study for Tolerance and Pharmacokinetic Characteristic of MAX-40279 in Patients With Relapsed or Refractory Acute Myelogenous Leukemia

Conditions
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AML

Intervention / Treatment
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* Drug: MAX-40279-01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and/or females over age 18. Subject has morphologically documented relapsed or refractoryprimary AML as defined by the World Health Organization (WHO) 2016 criteria for which no established standard therapy is available. ECOG performance status of 0 to 2. Persistent chronic clinically significant non-hematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1. Any anti-tumor treatment with radiation therapy, surgery, or immunotherapy wihtin 2 weeks prior to trial entry. Life expectancy of at least 3 months. Both men and women of reproductive potential must agree to use a highly effective method of birth control during the study and for six months following the last dose of study drug. Exclusion Criteria: Disease diagnosis of acute promyelocytic leukemia. Medical history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product. Previously treated malignancies other than the current disease, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years at the trial entry. Laboratory values not within the Protocol-defined range. Concomitant disease or condition that could interfere with the conduct of the trial, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAX-40279-01<br> | Drug: MAX-40279-01<br>* Part 1: Dose escalation, MAX-40279-01 twice daily with dose modifications based on tolerability criteria. Part 2: Dose expansion, Recommended doses from Part 1. For each dose level, a single dose of MAX-40279-01 will be first administered orally followed by 1 day observation, then continuous treatment will start 4 weeks treatment (per cycle).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) | Incidence of treatment-related AEs | 8 weeks | 
| Maximum tolerated dose (MTD） | MTD will be defined as the maximum dose level at which no more than 1 of 3 participants experience a dose-limiting toxicity (DLT) within the first 4 weeks of multiple dosing. | 4 weeks | 
| Phase II dose (RP2D) | The number and proportion of patients experiencing at least 1 dose-limiting toxicity (DLT) will be used as the primary measure to evaluate the RP2D of MAX-40279-01. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time to maximum plasma concentration | Approximately 4 weeks | 
| Cmax | Maximum plasma drug concentration | Approximately 4 weeks | 
| AUC | Area under the time-concentration curve | Approximately 4 weeks | 
| t1/2 | Observed terminal half-life | Approximately 4 weeks | 
| Objective response rate (ORR) | The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on IRWG. | 1 months (anticipated) |