TAK-243 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Refractory Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

Myelodysplastic Syndrome Clinical Trial

Official title: A Phase 1 Study of MLN7243 (TAK-243) for Either Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome/Chronic Myelomonocytic Leukemia Refractory to Hypomethylating Agents

Status Not yet recruiting

Clinical Trial Summary

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

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To establish the recommended phase 2 dose (RP2D) of ubiquitin-activating enzyme (UAE) inhibitor TAK-243 (MLN7243 [TAK-243]) administered intravenously in a twice-weekly schedule in patients with acute myeloid leukemia (AML) or patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) refractory to hypomethylating agents (HMAs).

SECONDARY OBJECTIVES:

I. To assess the maximum tolerated dose (MTD) evaluated on the first cycle (Day 1 to 21) of MLN7243 (TAK-243), its safety profile, and dose limiting toxicities (DLT).

II. To investigate preliminary anti-leukemic activity of MLN7243 (TAK-243) monotherapy in patients with AML, MDS and CMML.

III. To relate responses to the molecular/cytogenetic abnormalities in the malignant cells or to pharmacokinetic (PK)/pharmacodynamic (PD) findings.

IV. To describe the PK of MLN7243 (TAK-243). V. To describe the PD profile of MLN7243 (TAK-243) in the study population. VI. To establish the RP2D of MLN7243 (TAK-243) administered intravenously in a once-weekly schedule in patients with AML or patients with MDS or CMML refractory to HMAs.

OUTLINE: This is a dose escalation, followed by a dose expansion, study. Patients are assigned to 1 of 2 groups.

GROUP I: Patients receive UAE inhibitor TAK-243 intravenously (IV) over 10 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive UAE inhibitor TAK-243 IV over 10 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days. ;

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia
• Refractory Chronic Myelomonocytic Leukemia
• Refractory High Risk Myelodysplastic Syndrome
• Syndrome

• NCT number: NCT03816319
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: August 30, 2024
• Completion date: December 11, 2024