RECRUITING

TAK-243 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes With Increased Blasts

Conditions

Myelodysplastic Syndrome With Excess Blasts Recurrent Acute Myeloid Leukemia Recurrent Myelodysplastic Syndrome Recurrent Myelodysplastic Syndrome/Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Refractory Myelodysplastic Syndrome Refractory Myelodysplastic Syndrome/Acute Myeloid Leukemia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase I trial studies the side effects and best dose of TAK-243 in treating patients with acute myeloid leukemia or myelodysplastic syndromes with increased blasts that has come back (relapsed) or that is not responding to treatment (refractory). TAK-243 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Official Title

A Phase 1 Study of TAK-243 for Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes With Increased Blasts

Quick Facts

Study Start:2025-07-22

Study Completion:2026-10-24

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03816319

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Diagnosis of AML or MDS with increased blasts (MDS-IB) assessed by local laboratory review according to the 2022 World Health Organization (WHO) criteria for myeloid neoplasms. Both patients with MDS-IB1 (5-9% bone marrow blasts) and MDS-IB2 (10-19% bone marrow blasts) are eligible. * Patients must have relapsed or refractory disease after receiving at least one prior line of therapy * AML-specific	* Patients with acute promyelocytic leukemia (APL) or AML with t(15;17)(q22;q12) - PML::RARA). * Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1), except anemia, neutropenia or thrombocytopenia of any grade and grade 2 peripheral neuropathy. * Presence of any other malignancy requiring active therapy. * Patients who are receiving any other investigational agents. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAK-243. * Concomitant treatment with organic anion transport protein (OATP) and BCRP inhibitors or strong inducers/inhibitors of cytochrome P450 (CYP)3A4/5. Treatment with these agents must be discontinued at least 14 days prior to TAK-243 dosing. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. * Presence of an active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia. * Presence of active graft-versus-host disease (GVHD) or continued treatment with systemic immunosuppressive agents following allogeneic hematopoietic stem cell transplantation (HSCT). * Presence of any co-morbid condition that, in the opinion of the investigator, might compromise the patient's safety, might interfere with participation in the trial or might interfere with the interpretation of trial results. * Pregnant and lactating/breast-feeding women are excluded from this study because TAK-243 is a UAE-inhibiting agent with the potential for teratogenic or abortifacient effects and there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TAK-243. Females of child-bearing potential must have a negative serum pregnancy test within 7 days before enrollment and should not be lactating/breast-feeding. Breastfeeding should be discontinued if the mother is treated with TAK-243. * Major surgery within 14 days before the first dose of any study drug or a scheduled surgery during study period. * Patients with uncontrolled coagulopathy or bleeding disorder. * Patients with known hepatic cirrhosis. * Patients with known active cardiopulmonary disease defined as: * Unstable angina withing 3 months prior to first dose of TAK-243; * Myocardial infarction (MI) within 6 months prior to first dose of TAK-243 (patients who had MI and/or coronary revascularization more than 6 months before screening and who are without cardiac symptoms may enroll); * Congestive heart failure (New York Heart Association \[NYHA\] Class III or IV; * Cardiomyopathy with left ventricular ejection fraction (LVEF) \< 50%; * Symptomatic pulmonary hypertension. * Presence of active central nervous system (CNS) involvement (patients with prior CNS leukemia who have negative CNS cytology and who receive periodic prophylactic intrathecal chemotherapy are eligible). * Patients with clinically significant arrhythmia: * History of ventricular fibrillation or torsade de pointes at any time, * Episode of grade \>= 3 atrial fibrillation or flutter in the last 3 months, defined as symptomatic episode, requiring urgent intervention (cardioversion, pacemaker or ablation) or with life-threatening consequences. * Uncontrolled high blood pressure (i.e., systolic blood pressure \>180 mm Hg, diastolic blood pressure \> 95 mm Hg). * Prolonged rate corrected QT (QTc) interval \>= 480 msec, calculated using the Fridericia method. * Patients with known severe or very severe chronic obstructive pulmonary disease (defined as forced expiratory volume in one second (FEV1) less than 30% or less than 50% of predicted), interstitial lung disease, or pulmonary fibrosis. * Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s). * Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s). * Patients with history of neutrophilic dermatosis (e.g. Sweet syndrome, pyoderma gangrenosum), relapsing polychondritis, polyarteritis nodosa and/or giant cell arteritis. * Patients with VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome) or any other autoinflammatory disease.

Inclusion Criteria

Exclusion Criteria

* Diagnosis of AML or MDS with increased blasts (MDS-IB) assessed by local laboratory review according to the 2022 World Health Organization (WHO) criteria for myeloid neoplasms. Both patients with MDS-IB1 (5-9% bone marrow blasts) and MDS-IB2 (10-19% bone marrow blasts) are eligible.
* Patients must have relapsed or refractory disease after receiving at least one prior line of therapy
* AML-specific

* Patients with acute promyelocytic leukemia (APL) or AML with t(15;17)(q22;q12) - PML::RARA).
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1), except anemia, neutropenia or thrombocytopenia of any grade and grade 2 peripheral neuropathy.
* Presence of any other malignancy requiring active therapy.
* Patients who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAK-243.
* Concomitant treatment with organic anion transport protein (OATP) and BCRP inhibitors or strong inducers/inhibitors of cytochrome P450 (CYP)3A4/5. Treatment with these agents must be discontinued at least 14 days prior to TAK-243 dosing. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
* Presence of an active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
* Presence of active graft-versus-host disease (GVHD) or continued treatment with systemic immunosuppressive agents following allogeneic hematopoietic stem cell transplantation (HSCT).
* Presence of any co-morbid condition that, in the opinion of the investigator, might compromise the patient's safety, might interfere with participation in the trial or might interfere with the interpretation of trial results.
* Pregnant and lactating/breast-feeding women are excluded from this study because TAK-243 is a UAE-inhibiting agent with the potential for teratogenic or abortifacient effects and there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TAK-243. Females of child-bearing potential must have a negative serum pregnancy test within 7 days before enrollment and should not be lactating/breast-feeding. Breastfeeding should be discontinued if the mother is treated with TAK-243.
* Major surgery within 14 days before the first dose of any study drug or a scheduled surgery during study period.
* Patients with uncontrolled coagulopathy or bleeding disorder.
* Patients with known hepatic cirrhosis.
* Patients with known active cardiopulmonary disease defined as:
* Unstable angina withing 3 months prior to first dose of TAK-243;
* Myocardial infarction (MI) within 6 months prior to first dose of TAK-243 (patients who had MI and/or coronary revascularization more than 6 months before screening and who are without cardiac symptoms may enroll);
* Congestive heart failure (New York Heart Association \[NYHA\] Class III or IV;
* Cardiomyopathy with left ventricular ejection fraction (LVEF) \< 50%;
* Symptomatic pulmonary hypertension.
* Presence of active central nervous system (CNS) involvement (patients with prior CNS leukemia who have negative CNS cytology and who receive periodic prophylactic intrathecal chemotherapy are eligible).
* Patients with clinically significant arrhythmia:
* History of ventricular fibrillation or torsade de pointes at any time,
* Episode of grade \>= 3 atrial fibrillation or flutter in the last 3 months, defined as symptomatic episode, requiring urgent intervention (cardioversion, pacemaker or ablation) or with life-threatening consequences.
* Uncontrolled high blood pressure (i.e., systolic blood pressure \>180 mm Hg, diastolic blood pressure \> 95 mm Hg).
* Prolonged rate corrected QT (QTc) interval \>= 480 msec, calculated using the Fridericia method.
* Patients with known severe or very severe chronic obstructive pulmonary disease (defined as forced expiratory volume in one second (FEV1) less than 30% or less than 50% of predicted), interstitial lung disease, or pulmonary fibrosis.
* Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
* Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).
* Patients with history of neutrophilic dermatosis (e.g. Sweet syndrome, pyoderma gangrenosum), relapsing polychondritis, polyarteritis nodosa and/or giant cell arteritis.
* Patients with VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome) or any other autoinflammatory disease.

Contacts and Locations

Principal Investigator

Guillaume Richard-Carpentier

PRINCIPAL_INVESTIGATOR

University Health Network Princess Margaret Cancer Center LAO

Study Locations (Sites)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Guillaume Richard-Carpentier, PRINCIPAL_INVESTIGATOR, University Health Network Princess Margaret Cancer Center LAO

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-22

Study Completion Date2026-10-24

Study Record Updates

Study Start Date2025-07-22

Study Completion Date2026-10-24

Terms related to this study

Additional Relevant MeSH Terms

Myelodysplastic Syndrome With Excess Blasts
Recurrent Acute Myeloid Leukemia
Recurrent Myelodysplastic Syndrome
Recurrent Myelodysplastic Syndrome/Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia
Refractory Myelodysplastic Syndrome
Refractory Myelodysplastic Syndrome/Acute Myeloid Leukemia