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New treatment option for Myelodysplastic Syndrome With Excess Blasts
Official title TAK-243 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes With Increased Blasts
ClinicalTrials.gov ID: NCT03816319
What this study is testing
What is UAE Inhibitor TAK-243?
UAE Inhibitor TAK-243 is an investigational medicine, given as an once-weekly infusion into a vein, being studied as a potential treatment for myelodysplastic syndrome with excess blasts.
Also referred to as AOB87172, MLN7243.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
- Time commitment: about 12 months
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Diagnosis of AML or MDS with increased blasts (MDS-IB) assessed by local laboratory review according to the 2022 World Health Organization (WHO)...
- Patients must have relapsed or refractory disease after receiving at least one prior line of therapy
- AML-specific Patients with relapsed or refractory AML with \>= 5% bone marrow blasts after receiving at least two courses of intensive induction...
- MDS-specific Patients with relapsed or refractory MDS-IB with \>= 5% bone marrow blasts after at least 4 cycles of hypomethylating agent (HMA)-based...
- Patients must have recovered from the effects of any prior systemic therapy, radiotherapy or surgery:
You likely can't join if
- 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...
- 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...
See the full eligibility criteria
Who can join
- 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...
- Patients must have relapsed or refractory disease after receiving at least one prior line of therapy
- AML-specific Patients with relapsed or refractory AML with \>= 5% bone marrow blasts after receiving at least two courses of intensive induction chemotherapy (including, but not limited to, 7+3 regimen, fludarabine...
- MDS-specific Patients with relapsed or refractory MDS-IB with \>= 5% bone marrow blasts after at least 4 cycles of hypomethylating agent (HMA)-based therapy or at least two courses of intensive induction chemotherapy...
- 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 =\ = 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...
- 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 If they are of childbearing potential:
- 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...
- 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...
- 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...
- 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.
What rules you out
- 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...
- 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...
- 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...
- 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...
- 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...
- 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.
The study team makes the final eligibility decision.
Where it's taking place
- Tampa, Florida, United States
- Chicago, Illinois, United States
- Columbus, Ohio, United States
- Richmond, Virginia, United States
- Toronto, Ontario, Canada
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The study runs about 12 months per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Tampa, Florida, United States; Chicago, Illinois, United States; Columbus, Ohio, United States; Richmond, Virginia, United States; Toronto, Ontario, Canada. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.