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

NCT03816319 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2019-0023810237UM1CA186644
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose (RP2D)

  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).

  At 21 days

Secondary Outcomes (25)

• Incidence of adverse events

  Up to 30 days after the last dose of TAK-243

• Incidence of serious adverse events

  Up to 30 days after the last dose of TAK-243

• Incidence of dose-limiting toxicities (DLTs)

  Within the first cycle (Up to 21 days)

• Rate of complete response (CR) in patients with acute myeloid leukemia (AML)

  Up to 1 year

• Rate of complete response with incomplete hematological recovery (CRi), in patients with AML

  Up to 1 year

Study Arms (1)

Treatment (TAK-243)

EXPERIMENTAL

Patients receive TAK-243 IV over 30 minutes on days 1, 4, 8, and 11 of each cycle. Cycles repeats every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo urine sample collection, bone marrow aspiration and bone marrow biopsy, MUGA and ECHO during screening and on study, and blood sample collection throughout the trial.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Drug: UAE Inhibitor TAK-243

Interventions

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (TAK-243)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (TAK-243)

Biospecimen Collection PROCEDURE

Undergo urine and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (TAK-243)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (TAK-243)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (TAK-243)

UAE Inhibitor TAK-243 DRUG

Given IV

Also known as: AOB87172, MLN7243, TAK-243

Treatment (TAK-243)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify 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, 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;

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

SUSPENDED

MeSH Terms

Conditions

Anemia, Refractory, with Excess of Blasts; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Specimen Handling; Biopsy; TAK-243

Condition Hierarchy (Ancestors)

Anemia, Refractory; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Guillaume Richard-Carpentier

  University Health Network Princess Margaret Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: January 25, 2019
• Study Start: March 12, 2025
• Primary Completion (Estimated): October 24, 2026
• Study Completion (Estimated): October 24, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (4); CA (1)