Trial Filter

BETA

An intelligent search tool for clinical trials

Sign In
Back|NCT03850574Recruiting
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)

Phase
Phase 1/Phase 2
Sponsor
Aptose Biosciences Inc.
Enrollment
240
Timeline
Mar 2019 → Apr 2027
About This Study

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.

Eligibility Criteria

Inclusion Criteria

  • 1Study 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:
  • 2Refractory to at least 1 cycle of prior therapy
  • 3Relapsed after achieving remission with a prior therapy
  • 4Study participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • 5Study 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.
  • 6Study participant must meet the following criteria as indicated on the clinical laboratory tests.
  • 7Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3× institutional upper limit normal (ULN)
  • 8Total serum bilirubin ≤ 1.5× institutional ULN
  • 9Creatinine clearance as calculated by the Cockcroft-Gault formula or measured by 24-h urine collection of \> 45 mL/min.
  • 10Study participant is suitable for oral administration of study drug and has minimum life expectancy (≥ 3 months)
  • 11Female study participants must be either:
  • 12Of non-childbearing potential
  • 13Post-menopausal (defined as at least 1 year without any menses) prior to screening, or
  • 14Documented surgically sterile or status post hysterectomy (at least 1 month prior to screening)
  • 15Or, if of childbearing potential,
  • 16Must have a negative serum or urine pregnancy test at screening (within 72 hours prior to start of treatment), and
  • 17Must 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.
  • 18Female study participants must not be breastfeeding at screening and during the study period, and for 90 days after the final study drug administration
  • 19Female study participants must not donate ova starting at screening and throughout the study period, and for 90 days after the final study drug administration.
  • 20Male 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.
  • 21Male study participants must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
  • 22Study participant agrees not to participate in another interventional study while on treatment.
  • 23Study 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.
  • 24Study participants ≥ 75 years of age are considered ineligible to receive intensive chemotherapy if they meet any of the following criteria:
  • 25ECOG Performance Status of 2 or 3;
  • 26Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina;
  • 27Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume during the first second (FEV1) ≤ 65%;
  • 28Creatinine clearance ≥ 30 mL/min to \< 45 ml/min;
  • 29Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0×ULN;
  • 30Any 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.
  • 31Study participants are considered ineligible to receive intensive chemotherapy based on their age being ≥ 75 years.
  • 32Study participant \< 75 years has an ECOG performance status ≤ 2; study participant ≥ 75 years has an ECOG performance status 0-2.
  • 33Study participant must meet the following criteria as indicated on the clinical laboratory tests:
  • 34Serum AST and ALT ≤ 3× institutional ULN unless considered due to leukemic organ involvement.
  • 35Total 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.
  • 36Creatinine 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.
  • 37Study participant is suitable for oral administration of study drug and has minimum life expectancy (≥ 3 months)
  • 38Female study participants must be either:
  • 39Of non-childbearing potential
  • 40Post-menopausal (defined as at least 1 year without any menses) prior to screening, or
  • 41Documented surgically sterile or status post hysterectomy (at least 1 month prior to screening)
  • 42Or, if of childbearing potential,
  • 43Must have a negative serum or urine pregnancy test at screening (within 72 hours prior to start of treatment), and
  • 44Must use an acceptable highly effective contraception starting at screening and throughout the study period and for 90 days after the final study drug administration.
  • 45Female study participants must not be breastfeeding at screening and during the study period, and for 90 days after the final study drug administration.
  • 46Female study participants must not donate ova starting at screening and throughout the study period, and for 90 days after the final study drug administration.
  • 47Male 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.
  • 48Male study participants must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
  • 49Study participant agrees not to participate in another interventional study while on treatment.

Exclusion Criteria

  • 1Study participant was diagnosed with acute promyelocytic leukemia (APL).
  • 2Study participant has known BCR-ABL-positive leukemia.
  • 3Study participant has an active malignancy other than AML, MDS-IB2, or CMML.
  • 4Study 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)
  • 5Study participant has had hematopoietic stem cell transplant (HSCT) and meets any of the following criteria:
  • 6Has undergone HSCT within the 2-month period prior to the first study dose
  • 7Has clinically significant graft-versus-host-disease (GVHD) requiring treatment
  • 8Has ≥ Grade 2 persistent non-hematological toxicity related to the transplant
  • 9Had a donor lymphocyte infusion (DLI) ≤ 30 days prior to the first study dose.
  • 10Study participant has meningeal or central nervous system (CNS) involvement with leukemia or other CNS disease related to underlying and secondary effects of malignancy.
  • 11Study participant has disseminated intravascular coagulation abnormality (DIC).
  • 12Study participant has had major surgery within 4 weeks prior to the first study dose.
  • 13Study participant has had radiation therapy within 4 weeks prior to the first study dose.
  • 14Study 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%.
  • 15Study participant has any of the following cardiac abnormalities of history:
  • 16Study 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).
  • 17Study participant has a mean QT interval (QTc) by Friderica's method (QTcF) \> 450 ms in three successive screening measurements.
  • 18Study 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.
  • 19Study participant is known to have active infection including any identified active COVID-19 infection.
  • 20Study participant is known to have human immunodeficiency virus infection.
  • 21Study participant has known active hepatitis B or C, or other active hepatic disorder.
  • 22Study participant has any condition which, in the Investigator's opinion, makes the study participant unsuitable for study participation.
  • 23Study participant has a history of Grade 3 or 4 non-hematologic toxicity related to tyrosine kinase inhibitor.
  • 24Study participant was diagnosed with acute promyelocytic leukemia (APL).
  • 25Study participant has known BCR-ABL-positive leukemia.
  • 26Study participant has an active malignancy other than AML.
  • 27Study participant has received treatment with the following:
  • 28An 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.)
  • 29CAR-T cell therapy
  • 30Experimental therapies for antecedent myeloid neoplasms
  • 31Current participation in another research or observational study
  • 32Study 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).
  • 33Study participant has meningeal or central nervous system (CNS) involvement with leukemia or other CNS disease related to underlying and secondary effects of malignancy.
  • 34Study participant has disseminated intravascular coagulation abnormality (DIC).
  • 35Study participant has had major surgery within 4 weeks prior to the first study dose.
  • 36Study participant has had radiation therapy within 4 weeks prior to the first study dose.
  • 37Study 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%.
  • 38Study participant has any of the following cardiac abnormalities of history:
  • 39Study 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).
  • 40Study participant has a mean QT interval (QTc) by Friderica's method (QTcF) \> 450 ms in three successive screening measurements.
  • 41Study 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.
  • 42Study participant is known to have active infection, including any identified active COVID-19 infection.
  • 43Study participant is known to have human immunodeficiency virus infection.
  • 44Study participant has known active hepatitis B or C, or other active hepatic disorder.
  • 45Study 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.
  • 46Study 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.).
  • 47Study participant has a white blood cell count \> 25 × 10\^9/L. (Treatment with hydroxyurea or use of leukapheresis are permitted to meet this criterion.)

Locations

34 sites participating in this study

Emory University

Atlanta, Georgia 30322

Active, Not Recruiting

The Kirklin Clinic of UAB Hospital

Birmingham, Alabama 35233

Recruiting

Pankit Vachhani, MD

jsregister@uabmc.edu

City of Hope Comprehensive Cancer Center

Duarte, California 91010

Active, Not Recruiting
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →