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

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.

Study Overview

• Status: Recruiting
• Conditions: Leukemia, Myeloid, Acute; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome With Excess Blasts-2; Relapsed Adult AML; Refractory AML
• Intervention / Treatment: Drug: Tuspetinib; Drug: Venetoclax Oral Tablet; Drug: Azacitidine for Intravenous Infusion

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).

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rafael Bejar, MD, PhD; Phone Number: 858-401-6852; Email: rbejar@aptose.com

Study Locations

• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Active, not recruiting
      • Border Medical Oncology
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Active, not recruiting
      • Royal Brisbane and Women's Hospital
    • Townsville, Queensland, Australia, 4812
      • Active, not recruiting
      • Townsville University Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Active, not recruiting
      • St Vincent's Hospital Melbourne
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Active, not recruiting
      • Sir Charles Gairdner Hospital
• Germany
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Active, not recruiting
      • Universitätsklinikum Leipzig
  • State of Berlin
    • Berlin, State of Berlin, Germany, 13353
      • Active, not recruiting
      • Charité Universitätsmedizin Berlin
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1023
      • Active, not recruiting
      • Auckland City Hospital
• South Korea
  • Daegu, South Korea, 41944
    • Active, not recruiting
    • Kyungpook National University Hospital
  • Pusan, South Korea, 49241
    • Active, not recruiting
    • Pusan National University Hospital
  • Seongnam, South Korea, 13620
    • Active, not recruiting
    • Seoul National University Bundang Hospital
  • Seoul
    • Seoul, Seoul, South Korea, 03080
      • Completed
      • Seoul National University Hospital
    • Seoul, Seoul, South Korea, 05505
      • Active, not recruiting
      • Asan Medical Center
    • Seoul, Seoul, South Korea, 06351
      • Active, not recruiting
      • Samsung Medical Center
• Spain
  • Barcelona
    • Barcelona, Barcelona, Spain, 08035
      • Active, not recruiting
      • Hospital Universitario Vall d'Hebron
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Active, not recruiting
      • Hospital Quiron Madrid
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Active, not recruiting
      • Hospital Universitario Central de Asturias
  • Valencia
    • Valencia, Valencia, Spain, 46010
      • Active, not recruiting
      • Hospital Clínico Universitario de Valencia
    • Valencia, Valencia, Spain, 46026
      • Active, not recruiting
      • Hospital Universitari i Politecnic La Fe
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • The Kirklin Clinic of UAB Hospital
      • Contact: Pankit Vachhani, MD; Email: jsregister@uabmc.edu
  • California
    • Duarte, California, United States, 91010
      • Active, not recruiting
      • City of Hope Comprehensive Cancer Center
    • Irvine, California, United States, 92697
      • Recruiting
      • University of California Irvine
      • Principal Investigator: Deepa Jeyakumar, MD
      • Contact: Deepa Jeyakumar, MD; Email: djeyakum@hs.uci.edu
    • La Jolla, California, United States, 92093
      • Active, not recruiting
      • UCSD Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC/Norris Comprehensive Cancer Center
      • Contact: Eric Tam, MD; Email: eric.tam@med.usc.edu
      • Principal Investigator: Eric Tam, MD
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Cancer Center
      • Principal Investigator: Gabriel Mannis, MD
      • Contact: Gabriel Mannis, MD; Email: gmannis@stanford.edu
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California, Davis
      • Contact: Brian Jonas; Phone Number: (916) 703-9151; Email: bajonas@ucdavis.edu
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
      • Contact: Nikolai Podoltsev, MD; Email: nikolai.podoltsev@yale.edu
      • Principal Investigator: Nikolai Podoltsev, MD, PhD
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami - Miller School of Medicine
      • Contact: Justin Watts, MD; Email: jxw401@miami.edu
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Active, not recruiting
      • Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Active, not recruiting
      • Massachusetts General Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University Medical Center
      • Contact: Harry Erba, MD; Email: harry.erba@duke.edu
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Active, not recruiting
      • Cleveland Clinic - Taussig Cancer Center
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center
      • Principal Investigator: Uma Borate, MD
      • Contact: Uma Borate, MD; Email: uma.borate@osumc.edu
  • Texas
    • Huston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Naval Daver, Dr; Phone Number: 713-792-6477; Email: NDaver@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for Parts A/B/C:

• 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:

  1. Refractory to at least 1 cycle of prior therapy
  2. 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.

  1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3× institutional upper limit normal (ULN)
  2. Total serum bilirubin ≤ 1.5× institutional ULN
  3. 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

  1. Post-menopausal (defined as at least 1 year without any menses) prior to screening, or
  2. Documented surgically sterile or status post hysterectomy (at least 1 month prior to screening)

• Or, if of childbearing potential,

  1. Must have a negative serum or urine pregnancy test at screening (within 72 hours prior to start of treatment), and
  2. 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.

Exclusion Criteria for Parts A/B/C:

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:

  1. Has undergone HSCT within the 2-month period prior to the first study dose
  2. Has clinically significant graft-versus-host-disease (GVHD) requiring treatment
  3. Has ≥ Grade 2 persistent non-hematological toxicity related to the transplant
  4. 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:

  1. 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).
  2. Study participant has a mean QT interval (QTc) by Friderica's method (QTcF) > 450 ms in three successive screening measurements.
  3. 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.

Inclusion Criteria for Part D:

• 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:

1. ECOG Performance Status of 2 or 3;
2. Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina;
3. Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume during the first second (FEV1) ≤ 65%;
4. Creatinine clearance ≥ 30 mL/min to < 45 ml/min;
5. Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0×ULN;
6. 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:

  1. Serum AST and ALT ≤ 3× institutional ULN unless considered due to leukemic organ involvement.
  2. 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.
  3. 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

  1. Post-menopausal (defined as at least 1 year without any menses) prior to screening, or
  2. Documented surgically sterile or status post hysterectomy (at least 1 month prior to screening)

• Or, if of childbearing potential,

  1. Must have a negative serum or urine pregnancy test at screening (within 72 hours prior to start of treatment), and
  2. 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.

Exclusion Criteria for Part D:

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:

  1. 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.)
  2. CAR-T cell therapy
  3. Experimental therapies for antecedent myeloid neoplasms
  4. 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:

  1. 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).
  2. Study participant has a mean QT interval (QTc) by Friderica's method (QTcF) > 450 ms in three successive screening measurements.
  3. 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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Dose Escalation [COMPLETED]; Part 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.	Drug: Tuspetinib; Daily (QD), continuous dosing; Other Names: HM43239
Experimental: Part B Dose Exploration [ACTIVE, NOT RECRUITING]; Part B dose exploration of tuspetinib as a single agent is planned for up to 4 dose levels.	Drug: Tuspetinib; Daily (QD), continuous dosing; Other Names: HM43239
Experimental: Part C Dose Expansion (tuspetinib as a single agent) [COMPLETE]; Part 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.	Drug: Tuspetinib; Daily (QD), continuous dosing; Other Names: HM43239
Experimental: Part C Dose Expansion (tuspetinib plus venetoclax) [COMPLETE]; Part C dose expansion of tuspetinib in combination with venetoclax is planned for 2 dose levels. The initial tuspetinib dose will be 80 mg.	Drug: Tuspetinib; Daily (QD), continuous dosing; Other Names: HM43239; Drug: Venetoclax Oral Tablet; 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; Other Names: Venetoclax
Experimental: Part D Dose Exploration (tuspetinib plus venetoclax and azacitidine) [ACTIVE, RECRUITING - US Sites]; Part 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.	Drug: Tuspetinib; Daily (QD), continuous dosing; Other Names: HM43239; Drug: Venetoclax Oral Tablet; 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; Other Names: Venetoclax; Drug: Azacitidine for Intravenous Infusion; Azacitidine will be given to study participants in Part D as intravenous infusion at a dose of 75 mg/m^2; Other Names: Azacitidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of drug-related adverse events		4 years
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.	4 years
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.	Cycle 1 (at least 28 days)
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.	Cycle 1 (at least 28 days)
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.	Cycle 1 (at least 28 days)
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.	Cycle 1 (at least 28 days)
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.	Cycle 1 (at least 28 days)
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.	Cycle 1 (at least 28 days)
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.	Cycle 1 (at least 28 days)
Recommended Phase 2 dose (RP2D) of tuspetinib	The RP2D will be based on safety, efficacy, pharmacokinetic (PK), and pharmacodynamic (PD) considerations.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR)	Complete remission (CR) will be summarized using descriptive statistics.	4 years
Complete remission with partial hematologic recovery (CRh)	Complete remission with partial hematologic recovery (CRh) will be summarized using descriptive statistics.	4 years
Complete remission with incomplete platelet recovery (CRp)	Complete remission with incomplete platelet recovery (CRp) will be summarized using descriptive statistics.	4 years
Complete remission with incomplete hematologic recovery (CRi)	Complete remission with incomplete hematologic recovery (CRi) will be summarized using descriptive statistics.	4 years
Partial remission (PR)	Partial remission (PR) will be summarized using descriptive statistics.	4 years
Overall response rate	Overall response rate will be summarized using descriptive statistics.	4 years
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.	4 years
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.	4 years
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.	4 years
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.	4 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent inhibition of phosphorylation of targeted proteins	Flow cytometry will be used to identify leukemic blasts and quantify levels of phosphorylated targeted proteins including FLT3 and STAT5, among others, using a plasma inhibitory activity (PIA) assay that exposes cell lines to plasma from study participants treated in the study.	4 years
Mutation status of genes after treatment with tuspetinib	Mutation status of genes including, but limited to, FLT3, NRAS, and TP53	4 years

Collaborators and Investigators

• Sponsor: Aptose Biosciences Inc.
• Investigators: Principal Investigator: Naval Daver, MD, M.D. Anderson Cancer Center

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (Actual): February 22, 2019

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Relapsed; Refractory; AML; Venetoclax; Azacitidine; Newly Diagnosed; CMML; Chronic Myelomonocytic Leukemia; Tuspetinib; Myelodysplastic Syndromes with Increased Blasts Grade 2; MDS-IB2
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Drug Administration Routes; Drug Therapy; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Administration, Intravenous; Infusions, Parenteral; Azacitidine; venetoclax; Infusions, Intravenous
• Other Study ID Numbers: HM-FLTI-101; 2022-002826-29 (EudraCT Number); 2023-503244-14-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No