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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03850574
Other study ID # HM-FLTI-101
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date March 11, 2019
Est. completion date August 2024

Study information

Verified date October 2023
Source Aptose Biosciences Inc.
Contact Rafael Bejar, MD, PhD
Phone 858-401-6852
Email rbejar@aptose.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

A Phase 1/2, Open-label, Multicenter, Dose Escalation and Expansion Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Tuspetinib (HM43239) in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)


Description:

This is a Phase 1/2, open-label, multi-center study to assess the efficacy, safety, tolerability, pharmacokinetics, including recommended phase 2 dose (RP2D) of tuspetinib (HM43239) monotherapy in subjects with relapsed or treatment-refractory acute myeloid leukemia (AML). This study will also evaluate the safety, tolerability, and PK parameters of tuspetinib (HM43239) in combination with venetoclax when administered in patients with R/R AML


Recruitment information / eligibility

Status Recruiting
Enrollment 218
Est. completion date August 2024
Est. primary completion date February 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Patient is defined as having morphologically documented primary or secondary AML 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 - Patient has an Eastern Cooperative Oncology Group (ECOG) performance status = 2. - Patient'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 at 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, shorter than stated washout period may be considered provided that the patient has recovered from any clinically relevant safety issue and recovered to Grade = 1 toxicity from prior therapies) - Patient must meet the following criteria as indicated on the clinical laboratory tests 1. Serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) = 2.5× institutional upper limit normal (ULN) 2. Total serum bilirubin = 1.5× institutional ULN 3. Serum creatinine = 1.5× institutional ULN or an estimated glomerular filtration rate (eGFR) of > 45 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation. - Patient is suitable for oral administration of study drug and has minimum life expectancy (= 3 months) - Female patient must be either: - Of non-child bearing 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 highly effective contraception starting at screening and throughout the study period and for 90 days after the final study drug administration. - Female patient must not be breastfeeding at screening and during the study period, and for 90 days after the final study drug administration - Female patient must not donate ova starting at screening and throughout the study period, and for 90 days after the final study drug administration. - Male patient 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 patient must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration. - Patient agrees not to participate in another interventional study while on treatment Exclusion Criteria: Patients must not enter the study if any of the following exclusion criteria are fulfilled. - Patient was diagnosed as acute promyelocytic leukemia (APL) - Patient has BCR-ABL-positive leukemia - Patient has an active malignancy other than AML, or Myelodysplastic Syndrome (MDS). - Patient has persistent non-hematological toxicities of = Grade 2 (CTCAE v4.03), with symptoms and objective findings, from prior AML treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, or surgery) - Patient has had hematopoietic stem cell transplant (HSCT) and meets any of the following: 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. Has a donor lymphocytes infusion (DLI) = 30 days prior to the first study dose or during the first two cycle of treatment on the study. - Patient has meningeal or central nervous system (CNS) involvement with leukemia or other CNS disease related to underlying and secondary effects of malignancy. - Patient has disseminated intravascular coagulation abnormality (DIC). - Patient has had major surgery within 4 weeks prior to the first study dose. - Patient has had radiation therapy within 4 weeks prior to the first study dose. - Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patient 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%. - Any of the following cardiac abnormalities of history 1. Patient 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. Patient has a mean QT interval (QTc) by Friderica's method (QTcF) > 450ms in three successive Screening measurements. 3. Patient 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. 4. Patient is unable or unwilling to discontinue concomitant use of drugs that are known to prolong the QT interval. - Patient is known to have active infection including any identified active COVID-19 infection. - Patient is known to have human immunodeficiency virus infection. - Patient has known active hepatitis B or C, or other active hepatic disorder. - Patient has any condition which, in the investigator's opinion, makes the patient unsuitable for study participation. - Patient has a history of Grade 3 or 4 non-hematologic toxicity related to tyrosine kinase inhibitor.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Tuspetinib
Daily (QD), continuous dosing
Venetoclax Oral Tablet
Venetoclax will be given to patients in combo treatment group (Part C) either in 50 mg or 100 mg tablets

Locations

Country Name City State
Australia Border Medical Oncology Albury New South Wales
Australia St Vincent's Hospital Melbourne Fitzroy Victoria
Australia Royal Brisbane and Women's Hospital Herston Queensland
Australia Sir Charles Gairdner Hospital Nedlands Western Australia
Australia Townsville University Hospital Townsville Queensland
Germany Charité Universitätsmedizin Berlin Berlin
Germany Universitätsklinikum Leipzig Leipzig Saxony
Korea, Republic of Kyungpook National University Hospital Daegu
Korea, Republic of Pusan National University Hospital Pusan
Korea, Republic of Seoul National University Bundang Hospital Seongnam
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
New Zealand Auckland City Hospital Grafton Auckland
Spain Hospital Universitario Vall d'Hebron Barcelona
Spain Hospital Universitario Central de Asturias Oviedo Asturias
Spain Hospital Quirón Madrid Pozuelo De Alarcón Madrid
Spain Hospital Clinico Universitario de Valencia Valencia
Spain Hospital Universitari i Politècnic La Fe Valencia
United States Emory University Atlanta Georgia
United States The Kirklin Clinic of UAB Hospital Birmingham Alabama
United States Massachusetts General Hospital Boston Massachusetts
United States Cleveland Clinic - Taussig Cancer Center Cleveland Ohio
United States The Ohio State University Wexner Medical Center Columbus Ohio
United States City of Hope Comprehensive Cancer Center Duarte California
United States Duke University Medical Center Durham North Carolina
United States MD Anderson Cancer Center Houston Texas
United States University of California Irvine Irvine California
United States UCSD Moores Cancer Center La Jolla California
United States USC/Norris Comprehensive Cancer Center Los Angeles California
United States University of Miami - Miller School of Medicine Miami Florida
United States Yale University New Haven Connecticut
United States Stanford Cancer Center Palo Alto California
United States University of California, Davis Sacramento California

Sponsors (1)

Lead Sponsor Collaborator
Aptose Biosciences Inc.

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Korea, Republic of,  New Zealand,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Recommended Phase 2 dose To determine the recommended phase 2 dose based on safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) consideration 4 years
Primary Safety of HM43239 Determine the maximum tolerated dose at which no more than 1 out of 6 patients experience a dose-limiting toxicity or establish the safety of clinically effective dose below the MTD if the MTD is not reached.relapsed or treatment-refractory (R/R) AML 4 years
Primary Tolerability of HM43239 To determine the frequency and severity of drug-related adverse events across different dose levels when administered in patients with R/R AML 4 years
Primary Safety of HM43239 in combination with venetoclax Determine the maximum tolerated dose of HM43239 in combination with venetoclax at which no more than 1 out of 6 patients experience a dose-limiting toxicity or establish the safety of clinically effective dose below the MTD if the MTD is not reached.relapsed or treatment-refractory (R/R) AML 4 years
Primary Tolerability of HM43239 in combination with venetoclax To determine the frequency and severity of drug-related adverse events across different dose levels of HM43239 in combination with venetoclax when administered in patients with R/R AML 4 years
Secondary Anti-leukemic activity of HM43239 To investigate the rate of complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (CRi), and partial remission (PR) of patients taking HM43239 4 years
Secondary Anti-leukemic activity of HM43239 in combination with venetoclax To investigate the rate of complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (CRi), and partial remission (PR) of patients taking HM43239 in combination with venetoclax 4 years
Secondary Pharmacokinetic variables including maximum plasma concentration (Cmax) Pharmacokinetic variables including maximum plasma concentration (Cmax) Cycle 1 (at least 28 days)
Secondary Pharmacokinetic variables including minimum plasma concentration (Cmin) Pharmacokinetic variables including minimum plasma concentration (Cmin) Cycle 1 (at least 28 days)
Secondary Pharmacokinetic variables including area under the curve (AUC) Pharmacokinetic variables including area under the curve (AUC) Cycle 1 (at least 28 days)
Secondary Pharmacokinetic variables including volume of distribution Pharmacokinetic variables including volume of distribution Cycle 1 (at least 28 days)
Secondary Pharmacokinetic variables including clearance Pharmacokinetic variables including clearance Cycle 1 (at least 28 days)
Secondary Pharmacodynamic variables Determine PD variables by using a plasma inhibitory activity assay (PIA assay) examining the reduction in phospho-STAT5 and phospho-FLT3 in cell lines exposed to plasma from subjects treated in the study. 4 years
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