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Tuspetinib for Relapsed or Refractory Acute Myeloid Leukemia and Related Conditions

This study is testing a drug called tuspetinib (HM43239) for people with acute myeloid leukemia (AML), myelodysplastic syndromes with increased blasts grade 2 (MDS-IB2), or chronic myelomonocytic leukemia (CMML) that has come back or not responded to previous treatments. It's also for some newly diagnosed AML patients. Researchers want to find a safe and effective dose of tuspetinib, given alone or with other drugs like venetoclax or venetoclax plus azacitidine. The main goals are to see how safe tuspetinib is, what side effects it might cause, and how much of the drug stays in your body. Around 240 adults can join this study.

Study design
This is an open-label study, meaning you and your doctors will know which treatment you are receiving. It is a multi-center study, involving several locations, and aims to enroll about 240 participants.
What's involved
Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
The study will track the frequency and severity of drug-related side effects for up to 4 years.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT03850574

Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Recruiting
PHASE1Ages 18+InterventionalTreatment
Aptose Biosciences Inc.
~240 participants
Updated 2025-08-26 on ClinicalTrials.gov
What's tested:TuspetinibVenetoclax Oral TabletAzacitidine for Intravenous Infusion

At a glance

Recruiting sites
10 of 34 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Frequency and severity of drug-related adverse events
Measured over 4 years
+9 more outcomes measured

Conditions

Leukemia, Myeloid, Acute
Refractory AML
Relapsed Adult AML
Myelodysplastic Syndrome With Excess Blasts-2
Chronic Myelomonocytic Leukemia

Explore related trials

Acute Myeloid LeukemiaChronic Myelomonocytic LeukemiaMyelodysplastic Syndrome

Where it's being run

34 sites across 22 states
California6
Seoul3
South Korea3
Ohio2
Queensland2
Valencia2
Alabama1
Connecticut1

Study leadership

  • Naval Daver, MD · PRINCIPAL_INVESTIGATOR · M.D. Anderson Cancer Center

Who to contact

Rafael Bejar, MD, PhD
[email protected]
858-401-6852
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Study participant is defined as having morphologically documented primary or secondary AML, MDS-IB2 (≥ 10% bone marrow blasts), or CMML by the World Health Organization (WHO) criteria (2016), and fulfills one of the following:
Study participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Study participant's interval from prior treatment to time of study drug administration is at least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast cells), at 4 weeks for biologic or cellular immunotherapies, or least 5 half-lives for prior experimental agents or noncytotoxic agents, including immunosuppressive therapy post hematopoietic stem cell transplantation (HSCT). Upon discussion with the Medical Monitor, a shorter than stated washout period may be considered provided that the study participant has recovered from any clinically relevant safety issue and recovered to Grade ≤ 1 toxicity from prior therapies.
Study participant must meet the following criteria as indicated on the clinical laboratory tests.
Study participant is suitable for oral administration of study drug and has minimum life expectancy (≥ 3 months)
Female study participants must be either:
Of non-childbearing potential
Or, if of childbearing potential,
Female study participants must not be breastfeeding at screening and during the study period, and for 90 days after the final study drug administration
Female study participants must not donate ova starting at screening and throughout the study period, and for 90 days after the final study drug administration.
Male study participants and their female spouse/partners who are of childbearing potential must be using highly effective contraception starting at screening and continue throughout the study period and for 90 days after the final study drug administration.
Male study participants must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
Study participant agrees not to participate in another interventional study while on treatment.
Study participant is defined as having morphologically documented newly diagnosed previously untreated primary or secondary AML by the World Health Organization (WHO) criteria (2016) and considered ineligible to receive intensive chemotherapy.
Study participant \< 75 years has an ECOG performance status ≤ 2; study participant ≥ 75 years has an ECOG performance status 0-2.
Study participant must meet the following criteria as indicated on the clinical laboratory tests:
Study participant is suitable for oral administration of study drug and has minimum life expectancy (≥ 3 months)
Female study participants must be either:
Of non-childbearing potential
Or, if of childbearing potential,
Female study participants must not be breastfeeding at screening and during the study period, and for 90 days after the final study drug administration.
Female study participants must not donate ova starting at screening and throughout the study period, and for 90 days after the final study drug administration.
Male study participants and their female spouse/partners who are of childbearing potential must be using highly effective contraception starting at screening and continue throughout the study period and for 90 days after the final study drug administration.
Male study participants must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
Study participant agrees not to participate in another interventional study while on treatment.

Exclusion

Study participant was diagnosed with acute promyelocytic leukemia (APL).
Study participant has known BCR-ABL-positive leukemia.
Study participant has an active malignancy other than AML, MDS-IB2, or CMML.
Study participant has persistent non-hematological toxicities of ≥ Grade 2 (CTCAE v4.03), with symptoms and objective findings, from prior AML, MDS-IB2, or CMML treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, or surgery)
Study participant has had hematopoietic stem cell transplant (HSCT) and meets any of the following criteria:
Study participant has meningeal or central nervous system (CNS) involvement with leukemia or other CNS disease related to underlying and secondary effects of malignancy.
Study participant has disseminated intravascular coagulation abnormality (DIC).
Study participant has had major surgery within 4 weeks prior to the first study dose.
Study participant has had radiation therapy within 4 weeks prior to the first study dose.
Study participant has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or study participant with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.
Study participant has any of the following cardiac abnormalities of history:
Study participant is known to have active infection including any identified active COVID-19 infection.
Study participant is known to have human immunodeficiency virus infection.
Study participant has known active hepatitis B or C, or other active hepatic disorder.
Study participant has any condition which, in the Investigator's opinion, makes the study participant unsuitable for study participation.
Study participant has a history of Grade 3 or 4 non-hematologic toxicity related to tyrosine kinase inhibitor.
Study participant was diagnosed with acute promyelocytic leukemia (APL).
Study participant has known BCR-ABL-positive leukemia.
Study participant has an active malignancy other than AML.
Study participant has received treatment with the following:
Study participant has persistent non-hematological toxicities of ≥ Grade 2 (CTCAE v4.03), with symptoms and objective findings, from treatment for antecedent myeloid neoplasms (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, immunosuppressive therapy, radiation, or surgery).
Study participant has meningeal or central nervous system (CNS) involvement with leukemia or other CNS disease related to underlying and secondary effects of malignancy.
Study participant has disseminated intravascular coagulation abnormality (DIC).
Study participant has had major surgery within 4 weeks prior to the first study dose.
Study participant has had radiation therapy within 4 weeks prior to the first study dose.
Study participant has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or study participant with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.
Study participant has any of the following cardiac abnormalities of history:
Study participant is known to have active infection, including any identified active COVID-19 infection.
Study participant is known to have human immunodeficiency virus infection.
Study participant has known active hepatitis B or C, or other active hepatic disorder.
Study participant has any condition which, in the Investigator's opinion, makes the study participant unsuitable for study participation, including a chronic respiratory disease that requires continuous oxygen, or a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, or cardiovascular disease, or any other medical condition or known hypersensitivity to any of the study medications including excipients of VEN and AZA that in the opinion of the Investigator would adversely affect participating in this study.
Study participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal) or other medical conditions (e.g., infection, heart failure, COPD flare, etc.).
Study participant has a white blood cell count \> 25 × 10\^9/L. (Treatment with hydroxyurea or use of leukapheresis are permitted to meet this criterion.)

What this trial measures

  • Frequency and severity of drug-related adverse events4 years
  • Maximum tolerated dose (MTD) of tuspetinib4 years

    The MTD will be determined as the dose at which no more than 1 out of 6 study participants experiences a dose-limiting toxicity (DLT). Alternatively, the safety of a clinically effective dose below the MTD will be established if the MTD is not reached in study participants.

  • Maximum plasma concentration (Cmax)Cycle 1 (at least 28 days)

    Maximum plasma concentration (Cmax) will be summarized by cohort using descriptive statistics including number of study participants, mean, standard deviation, minimum, median, maximum, geometric mean, and coefficient of variation (CV) of the mean and geometric mean. Time-course of drug concentrations will be plotted as appropriate.

  • Minimum plasma concentration (Cmin)Cycle 1 (at least 28 days)

    Minimum plasma concentration (Cmin) will be summarized by cohort using descriptive statistics including number of study participants, mean, standard deviation, minimum, median, maximum, geometric mean, and coefficient of variation (CV) of the mean and geometric mean. Time-course of drug concentrations will be plotted as appropriate.

  • Area under the plasma concentration-time curve (AUC)Cycle 1 (at least 28 days)

    Area under the plasma concentration-time curve (AUC) for various timepoints will be summarized by cohort using descriptive statistics including number of study participants, mean, standard deviation, minimum, median, maximum, geometric mean, and coefficient of variation (CV) of the mean and geometric mean. Time-course of drug concentrations will be plotted as appropriate.

  • Time to maximum concentration (Tmax)Cycle 1 (at least 28 days)

    Time to maximum concentration (Tmax) will be summarized by cohort using descriptive statistics including number of study participants, mean, standard deviation, minimum, median, maximum, geometric mean, and coefficient of variation (CV) of the mean and geometric mean. Time-course of drug concentrations will be plotted as appropriate.

  • Terminal half-life (t1/2)Cycle 1 (at least 28 days)

    Terminal half-life (t1/2) will be summarized by cohort using descriptive statistics including number of study participants, mean, standard deviation, minimum, median, maximum, geometric mean, and coefficient of variation (CV) of the mean and geometric mean. Time-course of drug concentrations will be plotted as appropriate.

  • Volume of distributionCycle 1 (at least 28 days)

    Volume of distribution at various timepoints will be summarized by cohort using descriptive statistics including number of study participants, mean, standard deviation, minimum, median, maximum, geometric mean, and coefficient of variation (CV) of the mean and geometric mean. Time-course of drug concentrations will be plotted as appropriate.

  • Plasma clearance (CL)Cycle 1 (at least 28 days)

    Plasma clearance (CL) will be summarized by cohort using descriptive statistics including number of study participants, mean, standard deviation, minimum, median, maximum, geometric mean, and coefficient of variation (CV) of the mean and geometric mean. Time-course of drug concentrations will be plotted as appropriate.

  • Recommended Phase 2 dose (RP2D) of tuspetinib4 years

    The RP2D will be based on safety, efficacy, pharmacokinetic (PK), and pharmacodynamic (PD) considerations.