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Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients with Relapsed or Refractory Acute Myeloid Leukemia
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 details:
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).
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2019-03-11
Primary completion: 2026-11-01
Study completion finish: 2027-04-01
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT03850574
Intervention or treatment
DRUG: Tuspetinib
DRUG: Venetoclax Oral Tablet
DRUG: Azacitidine for Intravenous Infusion
Conditions
- • Leukemia, Myeloid, Acute
- • Refractory AML
- • Relapsed Adult AML
- • Myelodysplastic Syndrome With Excess Blasts-2
- • Chronic Myelomonocytic Leukemia
Find a site
Closest Location:
Sir Charles Gairdner Hospital
Research sites nearby
Select from list below to view details:
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia
Border Medical Oncology
Albury, New South Wales, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Townsville University Hospital
Townsville, Queensland, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Part A Dose Escalation [COMPLETED]
| DRUG: Tuspetinib
|
EXPERIMENTAL: Part B Dose Exploration [ACTIVE, NOT RECRUITING]
| DRUG: Tuspetinib
|
EXPERIMENTAL: Part C Dose Expansion (tuspetinib as a single agent) [ACTIVE, NOT RECRUITING]
| DRUG: Tuspetinib
|
EXPERIMENTAL: Part C Dose Expansion (tuspetinib plus venetoclax) [ACTIVE, NOT RECRUITING]
| DRUG: Tuspetinib
|
EXPERIMENTAL: Part D Dose Exploration (tuspetinib plus venetoclax and azacitidine) [ACTIVE, NOT RECRUITING]
| DRUG: Tuspetinib
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Frequency and severity of drug-related adverse events | Not Specified | 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
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome 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 |
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