NCT03850574 · Aptose Biosciences Inc.
Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia
(TUSCANY)
What this study is about
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
View original scientific description
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.
Interventions
DRUG
Tuspetinib
Daily (QD), continuous dosing
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
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
Primary outcome measures
Frequency and severity of drug-related adverse events
Time frame: 4 years
Maximum tolerated dose (MTD) of tuspetinib
Time frame: 4 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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 distribution
Time frame: Cycle 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)
Time frame: 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 tuspetinib
Time frame: 4 years
The RP2D will be based on safety, efficacy, pharmacokinetic (PK), and pharmacodynamic (PD) considerations.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 p
Where
- Birmingham, Alabama
- Duarte, California
- Irvine, California
- La Jolla, California
- Los Angeles, California
- Palo Alto, California
- Sacramento, California
- New Haven, Connecticut
- Miami, Florida
- Atlanta, Georgia
- Boston, Massachusetts
- Durham, North Carolina
And 3 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Aug 26, 2025 · Source of record for eligibility and locations