SuspendedPhase 1

Testing the Combination of Targeted Radiotherapy With Anti-Cancer Drugs, Venetoclax and ASTX-727, to Improve Outcomes for Adults With Newly Diagnosed Acute Myeloid Leukemia

Stopped: Drug Supply Issues

United States53 participantsStarted 2026-04-21

Plain-language summary

This phase I trial tests the safety, side effects, and best dose of lintuzumab-Ac225 in combination with venetoclax and ASTX-727, and how well they work in treating patients with newly diagnosed acute myeloid leukemia (AML). Lintuzumab-Ac225 is a monoclonal antibody, called lintuzumab, linked to a radioactive agent called actinium Ac 225. Lintuzumab attaches to CD33 positive cancer cells in a targeted way and delivers actinium Ac 225 to kill them. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. ASTX-727 is a combination of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Giving lintuzumab-Ac225 in combination with venetoclax and ASTX-727 may be safe and tolerable in treating patients with newly diagnosed AML and may improve the chance of going into remission and staying in remission for a longer period of time.

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Patients must have histologically or cytologically confirmed diagnosis of acute myeloid leukemia (AML) according to 2022 World Health Organization (WHO) criteria * Evidence of CD33 expression in more than 25% of bone marrow blasts by flow cytometry determined by local assessment * Patients must be considered ineligible for induction therapy defined by the following * ≥ 75 years of age; OR * \<75 years of age with at least one of the following co-morbidities or high-risk genetic features. Geriatric assessment and other tools to assess frailty have not been validated in patients with AML, and therefore will not be used to assess eligibility * Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3; * Cardiac history of congestive heart failure (CHF) requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina; * Diffusion capacity of lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%; * Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × upper limit of normal (ULN) * Patents with high risk genetic features based on local testing * inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) * t(3q26.2;v) * -5 or del(5q); -7; -17/abnormal(17p) * Complex karyotype or monosomal karyotype as defined by ELN 2022 * Mutated TP53 * Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of linituzumab-Ac-225 in …

What they're measuring

Incidence of dose limiting toxicities

Timeframe: Up to 28 days after the start of induction (up to 42 days for persistent neutropenia and thrombocytopenia)

Overall response rate (ORR)

Timeframe: Up to 5 years

Trial details

NCT IDNCT06802523

SponsorNational Cancer Institute (NCI)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2028-12-31