TAK-243 for Relapsed/Refractory AML or MDS
This study is testing TAK-243 in people with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) that has returned or isn't responding to treatment. TAK-243 may work by blocking enzymes that cancer cells need to grow. The main goal is to find the best dose of TAK-243 for future studies. You could be eligible if you are 18 or older and have AML or MDS with increased blasts, as diagnosed by specific WHO criteria. The study aims to enroll 42 participants, but its current status is unclear.
- Study design
- This is a dose-escalation study, meaning participants will receive increasing doses of TAK-243 to find the safest and most effective amount. It plans to enroll 42 participants.
- What's involved
- You would receive TAK-243 intravenously four times every 21-day cycle for up to 12 months. You will also have urine and blood samples taken, bone marrow procedures, and heart tests like ECHO and MUGA.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoint for determining the recommended dose is measured at 21 days, but treatment can continue for up to 12 months.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT03816319
TAK-243 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes With Increased Blasts
Suspended
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~42 participants
Updated 2026-08-27 on ClinicalTrials.gov
What's tested:Biospecimen CollectionBone Marrow AspirationBone Marrow BiopsyEchocardiography TestMultigated Acquisition ScanUAE Inhibitor TAK-243
At a glance
Recruiting sites
0 of 5 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Recommended phase II dose (RP2D)
Measured over At 21 days
Conditions
Where it's being run
5 sites across 5 statesFlorida1
Illinois1
Ohio1
Virginia1
Ontario1
Study leadership
- Guillaume Richard-Carpentier · PRINCIPAL_INVESTIGATOR · University Health Network Princess Margaret Cancer Center LAO
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
Patients must have recovered from the effects of any prior systemic therapy, radiotherapy or surgery:
Patients should not have received other investigational therapy within 2 weeks.
Patients should not have received standard chemotherapy within 1 week of administration of study drug; hydroxyurea administration (for leukocyte count control) is permitted.
Age \>=18 years. Because no dosing or adverse event data are currently available on the use of TAK-243 in patients \< 18 years of age, children are excluded from this study.
Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%).
Serum bilirubin =\< 1.5 × institutional upper limit of normal (ULN).
Patients with a known history of Gilbert's syndrome may enroll.
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 × institutional ULN.
Serum creatinine \< 176 mcmol/L (2 mg/dL) OR
Creatinine clearance ≥ 60 mL/min based on the Cockcroft-Gault equation.
Documented normal cardiac function (\>= 50%) by echocardiogram or multi-gated acquisition (MUGA) scan.
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load withing 6 months are eligible for this trial.
For patients with evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated.
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
The effects of TAK-243 on the developing human fetus are unknown and ubiquitin-activating enzyme inhibitors are known to be teratogenic. For this reason, female patients must be:
Postmenopausal (age-related amenorrhea \>= 12 consecutive months or follicle-stimulating hormone \> 40 mIU/mL), for at least 1 year before the screening visit, OR
Surgically sterile (i.e., who had undergone hysterectomy or bilateral oophorectomy), OR
Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), OR
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.) Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), OR
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Patients should have a minimum life expectancy of 1 month.
Exclusion
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.
What this trial measures
- Recommended phase II dose (RP2D)At 21 days
RP2D will be identified based on maximum tolerated dose and additional safety data. Primary endpoint will be analyzed on the population assessable for safety of the phase 1 trial (escalation part).