Acute Myelogenous Leukemia (AML)Phase 1NCT03412292
MAX-40279 in Subjects With Acute Myelogenous Leukemia (AML)
A Phase 1 study testing MAX-40279 in people with Acute Myelogenous Leukemia (AML), run by Maxinovel Pty., Ltd. at 4 sites in Australia.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia (AML)
- What is being tested?
- MAX-40279
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesAustralia
- Study dates
- 1 Aug 2018to 1 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- 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
Who cannot join
- 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
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- 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
- Legal incapacity or limited legal capacity
- 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
Trial locations and contacts
4 sites in 1 country.
Australia4 sites, 4 recruiting
- Recruiting
Monash Health
Clayton, Victoria, 3168
Uhe Micheleine, +6139594 4044
Jake Shortt
- Recruiting
St Vincent's Hospital Sydney Limited
Darlinghurst, New South Wales, 2010
Kent Robert
- Recruiting
Western NSW Local Health District
Dubbo, New South Wales, 2830
Millard Stephen
Douglas Lenton, DM
- Recruiting
Austin Health
Heidelberg, Victoria, 3084
Chun Fong
About this study
Official title: A Phase I Trial of MAX-40279 Given Orally to Subjects With Acute Myelogenous Leukemia (AML)
This is a dose-escalation phase I trial to evaluate the safety and tolerability of MAX-40279 in subjects with acute myelogenous leukemia(AML).
Read the detailed description
The class III receptor tyrosine kinase FMS-related tyrosine kinase 3 (FLT3), is mutated and activated in about 30% of adult patients with AML. The mutations involve either an internal tandem duplication (ITD) (in about 25% of AML patients) or a point mutation in the tyrosine kinase domain (TKD) (in about 7% of patients). Patients with mutations in FLT3, particularly those with ITD mutations, have a worse prognosis, with lower rate of complete remission, and lower overall survival . Thus, inhibition of activated FLT3 kinase by a pharmacologic agent is an attractive therapeutic strategy in AML.
The aberrant of fibroblast growth factor receptor (FGFR) might be a major reason fot resistance to targeted therapies, and FGFR inhibitors significantly suppress leukemia development in vivo.
MAX-40279 is a dual inhibitor of FLT3 and FGFR. Our goal is to develpe this uqiue dual inhibitor to be a more effective and wider use for AML treatment than the current known FLT3 inhibitors.
- Conditions
- Acute Myelogenous Leukemia (AML)
- Being tested
- MAX-40279
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MAX-40279Drug
Also called MAX-40279-001
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: MAX-40279 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (AEs)
Incidence of treatment-related AEs
Measured: 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.
Measured: 4 weeks
Secondary outcomes (6)
Tmax
Time to maximum plasma concentration
Measured: 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
Maximum plasma drug concentration
Measured: 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
Area under the time-concentration curve
Measured: 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
Observed terminal half-life
Measured: 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
To examine the phosphorylation (activation) of either wild-type or mutated Fms-like Tyrosine Kinase-3(FLT3)
Measured: First single dose(pre-dose), Cycle 1 Day 15(pre-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).
FGFR aberration
To detect Fibroblast growth factor receptor(FGFR) mutation
Measured: First single dose(pre-dose), Cycle 1 Day 15(pre-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start1 Aug 2018
- Primary completion1 Nov 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myelogenous Leukemia (AML)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maxinovel Pty., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03412292
- Sponsor's protocol ID
- Maxinovel
- Status last verified
- Jan 2022
- First submitted
- 8 Jan 2018
- Last updated
- 19 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of MAX-40279 Given Orally to Subjects With Acute Myelogenous Leukemia (AML)
- ClinicalTrials.gov ID
- NCT03412292
- Acronym / sponsor ID
- Maxinovel
- Conditions
- Acute Myelogenous Leukemia (AML)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Maxinovel Pty., Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 1 Nov 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 26 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a dose-escalation phase I trial to evaluate the safety and tolerability of MAX-40279 in subjects with acute myelogenous leukemia(AML).
Detailed description
The class III receptor tyrosine kinase FMS-related tyrosine kinase 3 (FLT3), is mutated and activated in about 30% of adult patients with AML. The mutations involve either an internal tandem duplication (ITD) (in about 25% of AML patients) or a point mutation in the tyrosine kinase domain (TKD) (in about 7% of patients). Patients with mutations in FLT3, particularly those with ITD mutations, have a worse prognosis, with lower rate of complete remission, and lower overall survival . Thus, inhibition of activated FLT3 kinase by a pharmacologic agent is an attractive therapeutic strategy in AML.
The aberrant of fibroblast growth factor receptor (FGFR) might be a major reason fot resistance to targeted therapies, and FGFR inhibitors significantly suppress leukemia development in vivo.
MAX-40279 is a dual inhibitor of FLT3 and FGFR. Our goal is to develpe this uqiue dual inhibitor to be a more effective and wider use for AML treatment than the current known FLT3 inhibitors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MAX-40279 | Experimental | Drug: MAX-40279MAX-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MAX-40279Also: MAX-40279-001MAX-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. | Drug | MAX-40279 |
Primary outcome
Adverse events (AEs)
Time frame: 8 weeks
Incidence of treatment-related AEs
Maximum tolerated dose (MTD)
Time frame: 4 weeks
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.
6 secondary outcomes
Tmax
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: First single dose(pre-dose), Cycle 1 Day 15(pre-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).
FGFR aberration
Time frame: First single dose(pre-dose), Cycle 1 Day 15(pre-dose), Cycle 1 Day 28(pre-dose), Cycle 2 Day 28(pre-dose).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MAX-40279 in people with Acute Myelogenous Leukemia (AML), run by Maxinovel Pty., Ltd. at 4 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chun Fong, MD (+61394965000, chun.fong@austin.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (AEs) (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2022.