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.
Eligibility criteria
Qualifiers
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 inclusion criteria: 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, cytarabine, idarubicin and filgrastim [FLAG-Ida] and mitoxantrone, etoposide, and cytarabine [MEC]) or 2 cycles of venetoclax-based lower intensity regimen (azacitidine plus venetoclax or low-dose cytarabine plus venetoclax), and without any other approved therapies available that would be more appropriate in the investigator's judgment. Patients who have received only one course of intensive induction chemotherapy but are not eligible for a second course because of decreased performance status or clear disease progression may be eligible for participation after discussion with the study principal investigator (PI). Patients with concomitant extramedullary disease relapse are eligible to participate, but not patients with isolated extramedullary relapse without bone marrow disease.
MDS-specific inclusion criteria: 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 and meet criteria for stable disease (SD), progressive disease (PD) or disease relapse according to the International Working Group 2023 response criteria for higher-risk MDS. Patients must not have access to any other approved therapies that would be more appropriate in the investigator's judgment. Patients who have received less than 4 cycles of HMA-based therapy may be eligible to participate after discussion with the study PI if there is clear evidence of progression or intolerance to HMA-based therapy that precludes its continuation.
Disqualifiers
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.