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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03412292




Registration number
NCT03412292
Ethics application status
Date submitted
8/01/2018
Date registered
26/01/2018
Date last updated
21/01/2019

Titles & IDs
Public title
MAX-40279 in Subjects With Acute Myelogenous Leukemia (AML)
Scientific title
A Phase I Trial of MAX-40279 Given Orally to Subjects With Acute Myelogenous Leukemia (AML)
Secondary ID [1] 0 0
Maxinovel
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myelogenous Leukemia (AML) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MAX-40279

Experimental: MAX-40279 - 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.


Treatment: Drugs: MAX-40279
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse events (AEs) - Incidence of treatment-related AEs
Timepoint [1] 0 0
8 weeks
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
4 weeks
Secondary outcome [1] 0 0
Tmax - Time to maximum plasma concentration
Timepoint [1] 0 0
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).
Secondary outcome [2] 0 0
Cmax - Maximum plasma drug concentration
Timepoint [2] 0 0
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).
Secondary outcome [3] 0 0
AUC - Area under the time-concentration curve
Timepoint [3] 0 0
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).
Secondary outcome [4] 0 0
t1/2 - Observed terminal half-life
Timepoint [4] 0 0
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).
Secondary outcome [5] 0 0
p-FLT3 Y591 - To examine the phosphorylation (activation) of either wild-type or mutated Fms-like Tyrosine Kinase-3(FLT3)
Timepoint [5] 0 0
First single dose(pre-dose), Cycle 1 Day 15(pre-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).
Secondary outcome [6] 0 0
FGFR aberration - To detect Fibroblast growth factor receptor(FGFR) mutation
Timepoint [6] 0 0
First single dose(pre-dose), Cycle 1 Day 15(pre-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).

Eligibility
Key inclusion criteria
1. Males and/or females over age 18

2. 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

3. 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

4. ECOG performance status of 0 to 2

5. Persistent chronic clinically significant nonhematological toxicities from prior
treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental
agents, radiation, HSCT, or surgery) must be Grade = 1

6. 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

7. 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;

8. Acceptable renal function defined below:

• Serum creatinine = 1.5 times ULN or calculated creatinine clearance (by the
Cockcroft-Gault formula) = 60 mL/min

9. Acceptable coagulation status defined below:

- Prothrombin time < 1.3 times ULN

- Partial thrombin time < 1.3 times ULN

10. No clinically significant abnormalities in urinalysis

11. Female participants of child bearing potential agree not to be pregnant or lactating
during the study and for three months following the last dose of study drug. Both men
and women of reproductive potential must agree to use a highly effective method of
birth control during the study and for three months following the last dose of study
drug. A highly effective method of contraception is defined as one that results in a
low failure rate, i.e., less than 1% per year, when used consistently and correctly
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Disease diagnosis of acute promyelocytic leukemia

2. 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

3. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy

4. Major surgery, other than diagnostic surgery, within 4 weeks prior to the trial entry,
without complete recovery

5. Percutaneous coronary intervention conducted within 6 months prior to the trial entry
for cardiac infarction or angina pectoris

6. Seizure disorders requiring anticonvulsant therapy

7. Taking a medication that prolongs QT interval and has a risk of Torsades de Pointes,or
a history of long QT syndrome

8. Medical history of difficulty swallowing, malabsorption or other chronic
gastrointestinal disease, or conditions that may hamper compliance and/or absorption
of the tested product

9. Participation in an investigational drug or device trial within 4 weeks prior to the
trial entry

10. Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

11. Recent venous thrombosis (including deep vein thrombosis or pulmonary embolism within
1 year of study)

12. History of upper gastrointestinal hemorrhage, peptic ulcer disease, or bleeding
diathesis

13. Subject is pregnant (positive serum beta human chorionic gonadotropin [ß-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

14. 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

15. Unwillingness or inability to comply with the trial protocol for any reason

16. Legal incapacity or limited legal capacity

17. Cardiac disease with New York Heart Association (NYHA) Class III or IV, including
congestive heart failure, myocardial infarction within 6 months prior to the trial
entry, unstable arrhythmia, or symptomatic peripheral arterial vascular

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney Limited - Darlinghurst
Recruitment hospital [2] 0 0
Western NSW Local Health District - Dubbo
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2830 - Dubbo
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Maxinovel Pty., Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT03412292
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Chun Fong, MD
Address 0 0
Country 0 0
Phone 0 0
+61394965000
Fax 0 0
Email 0 0
chun.fong@austin.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03412292