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AzTrials

Leukemia, Myeloid, AcutePhase 1/2TUSCANYNCT03850574

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

A Phase 1/2 study testing Tuspetinib, Venetoclax Oral Tablet and Azacitidine for Intravenous Infusion in people with Leukemia, Myeloid, Acute and Refractory AML, run by Aptose Biosciences Inc. at 34 sites in 6 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The main purpose of this study is to identify a safe and potentially effective dose of tuspetinib to be used in future studies in study participants diagnosed with acute myeloid leukemia (AML), myelodysplastic syndromes with increased blasts grade 2 (MDS-IB2), or chronic myelomonocytic leukemia (CMML) that is relapsed… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tuspetinib, Venetoclax Oral Tablet and Azacitidine for Intravenous Infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
240 participants
Where
34 sitesin 6 countries
Study dates
11 Mar 2019to Apr 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • 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:
  • Refractory to at least 1 cycle of prior therapy
  • Relapsed after achieving remission with a prior therapy
  • 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.
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  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3× institutional upper limit normal (ULN)
  • Total serum bilirubin ≤ 1.5× institutional ULN
  • Creatinine clearance as calculated by the Cockcroft-Gault formula or measured by 24-h urine collection of > 45 mL/min.
  • 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
  • Post-menopausal (defined as at least 1 year without any menses) prior to screening, or
  • Documented surgically sterile or status post hysterectomy (at least 1 month prior to screening)
  • Or, if of childbearing potential,
  • Must have a negative serum or urine pregnancy test at screening (within 72 hours prior to start of treatment), and
  • Must use an acceptable highly effective method of birth control starting at screening and throughout the study period and for 90 days after the final study drug administration.
  • 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 participants ≥ 75 years of age are considered ineligible to receive intensive chemotherapy if they meet any of the following criteria:
  • ECOG Performance Status of 2 or 3;
  • Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina;
  • Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume during the first second (FEV1) ≤ 65%;
  • Creatinine clearance ≥ 30 mL/min to < 45 ml/min;
  • Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0×ULN;
  • Any other comorbidity that the Investigator judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor during screening and prior to treatment.
  • Study participants are considered ineligible to receive intensive chemotherapy based on their age being ≥ 75 years.
  • 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:
  • Serum AST and ALT ≤ 3× institutional ULN unless considered due to leukemic organ involvement.
  • Total serum bilirubin ≤ 3x institutional ULN unless considered due to leukemic organ involvement for study participants < 75 years; total serum bilirubin ≤ 1.5x institutional ULN (or ≤ 3x institutional ULN if documented history of Gilbert's syndrome) unless considered due to leukemic organ involvement for study participants ≥ 75 years.
  • Creatinine clearance as calculated by the Cockcroft-Gault formula or measured by 24-h urine collection of ≥ 30 mL/min for study participants < 75 years; creatinine clearance as calculated by the Cockcroft-Gault formula or measured by 24-h urine collection of ≥ 45 mL/min for study participants ≥ 75 years.
  • 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
  • Post-menopausal (defined as at least 1 year without any menses) prior to screening, or
  • Documented surgically sterile or status post hysterectomy (at least 1 month prior to screening)
  • Or, if of childbearing potential,
  • Must have a negative serum or urine pregnancy test at screening (within 72 hours prior to start of treatment), and
  • Must use an acceptable highly effective contraception starting at screening and throughout the study period and for 90 days after the final study drug administration.
  • 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.

Who cannot join

  • Study participants must not enter the study if any of the following exclusion criteria are met:
  • 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:
Show all 49Show fewer
  • Has undergone HSCT within the 2-month period prior to the first study dose
  • Has clinically significant graft-versus-host-disease (GVHD) requiring treatment
  • Has ≥ Grade 2 persistent non-hematological toxicity related to the transplant
  • Had a donor lymphocyte infusion (DLI) ≤ 30 days prior to the first study dose.
  • 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 has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms).
  • Study participant has a mean QT interval (QTc) by Friderica's method (QTcF) > 450 ms in three successive screening measurements.
  • Study participant has any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as congenital long QT, syndrome, family history of long QT syndrome.
  • 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 participants must not enter the study if any of the following exclusion criteria are met:
  • 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:
  • An HMA, VEN (or other BCL-2 inhibitor), a tyrosine kinase inhibitor (TKI), a FLT3 inhibitor (FLT3i), a hematopoietic stem cell transplant (HSCT), and/or a chemotherapeutic agent for antecedent myeloid neoplasm (Note: Prior chemotherapy for solid tumors considered in remission is allowed.)
  • CAR-T cell therapy
  • Experimental therapies for antecedent myeloid neoplasms
  • Current participation in another research or observational study
  • 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 has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms).
  • Study participant has a mean QT interval (QTc) by Friderica's method (QTcF) > 450 ms in three successive screening measurements.
  • Study participant has any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as congenital long QT, syndrome, family history of long QT syndrome.
  • 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.)

Trial locations and contacts

34 sites in 6 countries. Contact the study team or a site near you to ask about taking part.

Rafael Bejar, MD, PhD contact

858-401-6852

rbejar@aptose.com

34 sites in 6 countries

United States15 sites, 10 recruiting

  • Emory University

    Atlanta, Georgia, 30322

    Active, not recruiting

  • The Kirklin Clinic of UAB Hospital

    Birmingham, Alabama, 35233

    Pankit Vachhani, MD, jsregister@uabmc.edu

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Active, not recruiting

  • Cleveland Clinic - Taussig Cancer Center

    Cleveland, Ohio, 44106

    Active, not recruiting

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

    Uma Borate, MD, uma.borate@osumc.edu

    Uma Borate, MD

    Recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

    Active, not recruiting

  • Duke University Medical Center

    Durham, North Carolina, 27705

    Harry Erba, MD, harry.erba@duke.edu

    Recruiting

  • MD Anderson Cancer Center

    Huston, Texas, 77030

    Naval Daver, Dr, 713-792-6477, NDaver@mdanderson.org

    Recruiting

  • University of California Irvine

    Irvine, California, 92697

    Deepa Jeyakumar, MD, djeyakum@hs.uci.edu

    Deepa Jeyakumar, MD

    Recruiting

  • UCSD Moores Cancer Center

    La Jolla, California, 92093

    Active, not recruiting

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

    Eric Tam, MD, eric.tam@med.usc.edu

    Eric Tam, MD

    Recruiting

  • University of Miami - Miller School of Medicine

    Miami, Florida, 33136

    Justin Watts, MD, jxw401@miami.edu

    Recruiting

  • Yale University

    New Haven, Connecticut, 06520

    Nikolai Podoltsev, MD, nikolai.podoltsev@yale.edu

    Nikolai Podoltsev, MD, PhD

    Recruiting

  • Stanford Cancer Center

    Palo Alto, California, 94304

    Gabriel Mannis, MD, gmannis@stanford.edu

    Gabriel Mannis, MD

    Recruiting

  • University of California, Davis

    Sacramento, California, 95817

    Brian Jonas, (916) 703-9151, bajonas@ucdavis.edu

    Recruiting

Other trials in United States

South Korea6 sites

  • Kyungpook National University Hospital

    Daegu, 41944

    Active, not recruiting

  • Pusan National University Hospital

    Pusan, 49241

    Active, not recruiting

  • Seoul National University Bundang Hospital

    Seongnam, 13620

    Active, not recruiting

  • Seoul National University Hospital

    Seoul, Seoul, 03080

    Completed

  • Asan Medical Center

    Seoul, Seoul, 05505

    Active, not recruiting

  • Samsung Medical Center

    Seoul, Seoul, 06351

    Active, not recruiting

Other trials in South Korea

Australia5 sites

  • Border Medical Oncology

    Albury, New South Wales, 2640

    Active, not recruiting

  • St Vincent's Hospital Melbourne

    Fitzroy, Victoria, 3065

    Active, not recruiting

  • Royal Brisbane and Women's Hospital

    Herston, Queensland, 4006

    Active, not recruiting

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

    Active, not recruiting

  • Townsville University Hospital

    Townsville, Queensland, 4812

    Active, not recruiting

Other trials in Australia

Spain5 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, Barcelona, 08035

    Active, not recruiting

  • Hospital Universitario Central de Asturias

    Oviedo, Principality of Asturias, 33011

    Active, not recruiting

  • Hospital Quirón Madrid

    Pozuelo de Alarcón, Madrid, 28223

    Active, not recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia, Valencia, 46010

    Active, not recruiting

  • Hospital Universitari i Politècnic La Fe

    Valencia, Valencia, 46026

    Active, not recruiting

Other trials in Spain

Germany2 sites

  • Charité Universitätsmedizin Berlin

    Berlin, State of Berlin, 13353

    Active, not recruiting

  • Universitätsklinikum Leipzig

    Leipzig, Saxony, 04103

    Active, not recruiting

Other trials in Germany

New Zealand1 site

  • Auckland City Hospital

    Grafton, Auckland, 1023

    Active, not recruiting

Other trials in New Zealand

About this study

Official title: A Phase 1/2 Open Label, Multicenter, Dose Escalation and Expansion Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM43239 in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

The main purpose of this study is to identify a safe and potentially effective dose of tuspetinib to be used in future studies in study participants diagnosed with acute myeloid leukemia (AML), myelodysplastic syndromes with increased blasts grade 2 (MDS-IB2), or chronic myelomonocytic leukemia (CMML) that is relapsed or refractory after at least one line of prior therapy, or in study participants with newly diagnosed AML. Tuspetinib will be administered as a single agent or in combination with other drugs (venetoclax or venetoclax plus azacitidine), as specified for each part of the study.

Read the detailed description

This is a Phase 1/2, open-label, multi-center study designed to assess the efficacy, safety, tolerability, and pharmacokinetics, including determining the recommended Phase 2 dose (RP2D) of tuspetinib (HM43239) in subjects with relapsed or treatment-refractory acute myeloid leukemia (AML).

Part C: This portion of the study will evaluate tuspetinib (HM43239) as monotherapy in patients with relapsed or refractory (R/R) AML, focusing on safety, tolerability, pharmacokinetics, and preliminary efficacy (Aptivate).

Part D: This portion of the study will evaluate the safety, tolerability, and PK parameters of tuspetinib (HM43239) in combination with venetoclax and azacitidine when administered to newly diagnosed AML patients who are ineligible for induction chemotherapy (Tuscany).

Being tested
Tuspetinib, Venetoclax Oral Tablet, Azacitidine for Intravenous Infusion
Keywords
Tuspetinib, Acute Myeloid Leukemia, AML, Relapsed, Refractory, Myelodysplastic Syndromes with Increased Blasts Grade 2, MDS-IB2, Chronic Myelomonocytic Leukemia, CMML, Venetoclax, Azacitidine, Newly Diagnosed
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TuspetinibDrug

    Also called HM43239

    Daily (QD), continuous dosing

  • Venetoclax Oral TabletDrug

    Also called Venetoclax

    Venetoclax will be given to study participants in the Part C tuspetinib plus venetoclax combination treatment group either in 50 mg or 100 mg tablets

  • Azacitidine for Intravenous InfusionDrug

    Also called Azacitidine

    Azacitidine will be given to study participants in Part D as intravenous infusion at a dose of 75 mg/m^2

Study groups in NCT03850574
Study groupRoleWhat they receive
Part A Dose Escalation [COMPLETED]ExperimentalPart A dose escalation of tuspetinib as a single agent is planned for up to 6 dose levels. If a study participant in dose escalation at any dose level achieves clinical response, then the dose level will continue to enroll in Part B. If one DLT or less is observed in the 6 participants (<1/6 DLT observed) in Part A, up to 20 evaluable participants can be enrolled in Part B at that dose level.
Receives: Drug: Tuspetinib
Part B Dose Exploration [ACTIVE, NOT RECRUITING]ExperimentalPart B dose exploration of tuspetinib as a single agent is planned for up to 4 dose levels.
Receives: Drug: Tuspetinib
Part C Dose Expansion (tuspetinib as a single agent) [COMPLETE]ExperimentalPart C dose expansion of tuspetinib as a single agent is planned for 2 dose levels. Study participants will be randomly assigned to either arm based on the number of slots available. The initial tuspetinib dose will be 120 mg.
Receives: Drug: Tuspetinib
Part C Dose Expansion (tuspetinib plus venetoclax) [COMPLETE]ExperimentalPart C dose expansion of tuspetinib in combination with venetoclax is planned for 2 dose levels. The initial tuspetinib dose will be 80 mg.
Receives: Drug: Tuspetinib; Drug: Venetoclax Oral Tablet
Part D Dose Exploration (tuspetinib plus venetoclax and azacitidine) [ACTIVE, RECRUITING - US Sites]ExperimentalPart D dose exploration of tuspetinib in combination with venetoclax and azacitidine is planned for up to 6 dose levels. The initial tuspetinib dose will be 40 mg.
Receives: Drug: Tuspetinib; Drug: Venetoclax Oral Tablet; Drug: Azacitidine for Intravenous Infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency and severity of drug-related adverse events

    Measured: 4 years

  2. Maximum tolerated dose (MTD) of tuspetinib

    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.

    Measured: 4 years

  3. Maximum plasma concentration (Cmax)

    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.

    Measured: Cycle 1 (at least 28 days)

  4. Minimum plasma concentration (Cmin)

    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.

    Measured: Cycle 1 (at least 28 days)

  5. Area under the plasma concentration-time curve (AUC)

    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.

    Measured: Cycle 1 (at least 28 days)

  6. Time to maximum concentration (Tmax)

    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.

    Measured: Cycle 1 (at least 28 days)

  7. Terminal half-life (t1/2)

    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.

    Measured: Cycle 1 (at least 28 days)

  8. Volume of distribution

    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.

    Measured: Cycle 1 (at least 28 days)

  9. Plasma clearance (CL)

    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.

    Measured: Cycle 1 (at least 28 days)

  10. Recommended Phase 2 dose (RP2D) of tuspetinib

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

    Measured: 4 years

Secondary outcomes (10)

  1. Complete remission (CR)

    Complete remission (CR) will be summarized using descriptive statistics.

    Measured: 4 years

  2. Complete remission with partial hematologic recovery (CRh)

    Complete remission with partial hematologic recovery (CRh) will be summarized using descriptive statistics.

    Measured: 4 years

  3. Complete remission with incomplete platelet recovery (CRp)

    Complete remission with incomplete platelet recovery (CRp) will be summarized using descriptive statistics.

    Measured: 4 years

  4. Complete remission with incomplete hematologic recovery (CRi)

    Complete remission with incomplete hematologic recovery (CRi) will be summarized using descriptive statistics.

    Measured: 4 years

  5. Partial remission (PR)

    Partial remission (PR) will be summarized using descriptive statistics.

    Measured: 4 years

  6. Overall response rate

    Overall response rate will be summarized using descriptive statistics.

    Measured: 4 years

  7. Duration of response

    Survival curves and median for time-to-event variables will be estimated using the Kaplan-Meier method and will be reported along with corresponding 95% confidence intervals.

    Measured: 4 years

  8. Disease-free survival (DFS)

    Survival curves and median for time-to-event variables will be estimated using the Kaplan-Meier method and will be reported along with corresponding 95% confidence intervals.

    Measured: 4 years

  9. Overall survival (OS)

    Survival curves and median for time-to-event variables will be estimated using the Kaplan-Meier method and will be reported along with corresponding 95% confidence intervals.

    Measured: 4 years

  10. Event-free survival (EFS)

    Survival curves and median for time-to-event variables will be estimated using the Kaplan-Meier method and will be reported along with corresponding 95% confidence intervals.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2019
  2. Study start11 Mar 2019
  3. Primary completionNov 2026 (estimated)
  4. Study completionApr 2027 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
1. Part A: Tuspetinib dose escalation 2. Part B: Tuspetinib dose exploration 3. Part C: Tuspetinib monotherapy dose expansion 4. Part C: Tuspetinib in combination with venetoclax ("doublet" therapy) dose expansion 5. Part D: Tuspetinib in combination with venetoclax and azacitidine ("triplet" therapy) dose exploration
Masking
None (open label)
Enrolment
240 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03850574
Sponsor's protocol ID
HM-FLTI-101
Other IDs
2023-503244-14-00, 2022-002826-29, 2023
Acronym
TUSCANY
Status last verified
Aug 2025
First submitted
28 Jan 2019
Last updated
26 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Sonowal H, Rice WG, Bejar R, Byun JY, Jung SH, Sinha R, Howell SB. Preclinical Development of Tuspetinib for the Treatment of Acute Myeloid Leukemia. Cancer Res Commun. 2025 Jan 1;5(1):74-83. doi: 10.1158/2767-9764.CRC-24-0258.

    PubMed 39665627

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tuspetinib, Venetoclax Oral Tablet and Azacitidine for Intravenous Infusion in people with Leukemia, Myeloid, Acute and Refractory AML, run by Aptose Biosciences Inc. at 34 sites in 6 countries.

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 49 inclusion and 49 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: looking for participants now, as of the sponsor's last update on 26 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, South Korea, Australia, Spain, Germany and 1 more country. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Rafael Bejar, MD, PhD (858-401-6852, rbejar@aptose.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency and severity of drug-related adverse events (time frame: 4 years). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03850574, which also lists 1 linked publication.

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 26 Aug 2025.

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