MAX-40279 in Subjects With Acute Myelogenous Leukemia (AML)

NCT03412292 | Unknown Phase 1

• 1 other identifier: Maxinovel
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

This is a dose-escalation phase I trial to evaluate the safety and tolerability of MAX-40279 in subjects with acute myelogenous leukemia(AML).

Conditions

Acute Myelogenous Leukemia (AML)

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (6)

• Tmax

  First single dose(pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24h post-dose), Cycle 1 Day 1 (the second dose)(pre-dose),Cycle 1 Day 15(pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24h post-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).

• Cmax

  First single dose(pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24h post-dose), Cycle 1 Day 1 (the second dose)(pre-dose),Cycle 1 Day 15(pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24h post-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).

• AUC

  First single dose(pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24h post-dose), Cycle 1 Day 1 (the second dose)(pre-dose),Cycle 1 Day 15(pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24h post-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).

• t1/2

  First single dose(pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24h post-dose), Cycle 1 Day 1 (the second dose)(pre-dose),Cycle 1 Day 15(pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24h post-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).

• p-FLT3 Y591

  First single dose(pre-dose), Cycle 1 Day 15(pre-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).

Study Arms (1)

MAX-40279

EXPERIMENTAL

MAX-40279 is provided as a capsule for oral use at 5mg, 25mg. In the dose-escalation phase, patients will be enrolled sequentially into the 5 dose levels of MAX-40279 designated in this study: 20, 40, 70, 100 and 120 mg/day (3-6 patients per cohort),bid.For each dose level, a single dose of MAX-40279 will be first administered orally followed by 1 day observation, then continuous treatment will start 4 weeks treatment (per cycle). After completion of the dose escalation, additional patients will be enrolled into dose expansion at the Maximum tolerated dose(MTD), up to 12 patients will be enrolled into expansion cohorts.

Drug: MAX-40279

Interventions

MAX-40279 DRUG

MAX-40279, is a multi-targeted kinase inhibitor inhibitor mainly target FLT3 and FGFR. It has a molecular weight of 496.56 Daltons, which has a formula of C24H25FN6O3S. MAX-40279 is yellow powder. It is insoluble in water, methanol, ethanol, 0.1 mol/L hydrochloride solution or 0.1% saline; very slightly soluble in methylene dichloride and sparingly soluble in dimethylformamide. It is stable under strong acid, strong alkali, high temperatures and exposure to light. MAX-40279 for clinical use is presented as a sterile yellow powder packaged in capsules at 5 mg, or 25 mg doses.

Also known as: MAX-40279-001

MAX-40279

Eligibility Criteria

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

You may qualify if:

• Males and/or females over age 18
• Ability to understand the purposes and risks of the trial and signed informed consent forms approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC) of the trial site was obtained before the entering the trial
• Subject has morphologically documented primary AML or AML secondary to myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria for which no established standard therapy is available
• ECOG performance status of 0 to 2
• Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1
• In the absence of rapidly progressing disease clearly documented by the investigator, the interval from prior treatment to time of MAX-40279 administration will be at least 2 weeks (14 days) for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT
• Acceptable liver function defined below:
• Total bilirubin ≤ 1.5 times upper limit of normal range (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times ULN;
• Acceptable renal function defined below:
• Serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance (by the Cockcroft-Gault formula) ≥ 60 mL/min
• Acceptable coagulation status defined below:
• Prothrombin time \< 1.3 times ULN
• Partial thrombin time \< 1.3 times ULN
• No clinically significant abnormalities in urinalysis

You may not qualify if:

• Disease diagnosis of acute promyelocytic leukemia
• 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
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Major surgery, other than diagnostic surgery, within 4 weeks prior to the trial entry, without complete recovery
• Percutaneous coronary intervention conducted within 6 months prior to the trial entry for cardiac infarction or angina pectoris
• Seizure disorders requiring anticonvulsant therapy
• Taking a medication that prolongs QT interval and has a risk of Torsades de Pointes，or a history of long QT syndrome
• Medical history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product
• Participation in an investigational drug or device trial within 4 weeks prior to the trial entry
• Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Recent venous thrombosis (including deep vein thrombosis or pulmonary embolism within 1 year of study)
• History of upper gastrointestinal hemorrhage, peptic ulcer disease, or bleeding diathesis
• Subject is pregnant (positive serum beta human chorionic gonadotropin \[β-HCG\] test at screening) or is currently breast-feeding, their partner anticipates becoming pregnant/impregnating during the trial or within 6 months after receiving the last dose of trial treatment
• 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
• Unwillingness or inability to comply with the trial protocol for any reason

Sponsors & Collaborators

• Maxinovel Pty., Ltd.: lead

Study Sites (4)

St Vincent's Hospital Sydney Limited

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Western NSW Local Health District

Dubbo, New South Wales, 2830, Australia

RECRUITING

Monash Health

Clayton, Victoria, 3168, Australia

RECRUITING

Austin Health

Heidelberg, Victoria, 3084, Australia

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Chun Fong, MD

CONTACT

+61394965000; chun.fong@austin.org.au

Hanying Bao, MD,Ph.D

CONTACT

+86-021-51370693; hybao@maxinovel.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: January 8, 2018
• First Posted: January 26, 2018
• Study Start: August 1, 2018
• Primary Completion: November 1, 2022
• Study Completion: December 1, 2022
• Last Updated: January 19, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)