NCT06802523

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

A Phase I Study of Lintuzumab-Ac-225 in Combination With Venetoclax and ASTX-727 in Adults With Newly Diagnosed AML

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 53 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. To determine recommended phase 2 dose (RP2D) of actinium Ac 225 lintuzumab (lintuzumab-Ac225) when used in combination with venetoclax and decitabine and cedazuridine (ASTX-727). SECONDARY OBJECTIVES: I. To determine the maximum tolerated dose of lintuzumab-Ac225 when used in combination with venetoclax and ASTX-727. II. To describe the frequency and severity of adverse events of patients treated on study, including cytopenia and organ toxicity after second dose of lintuzumab-Ac225. III. To determine the rate and time to complete remission (CR), complete remission with incomplete hematologic recovery (Cri), and complete remission with partial hematologic recovery (CRh). IV. To determine the rate and time to achieve CR/Cri/CRh without minimal residual disease (MRD) by multiparameter flow cytometry (MFC). V. To determine the duration of remission, event-free and overall survival of patients. VI. To evaluate and compare the clinical activity and toxicity between two lintuzumab-Ac225 administration schedules. EXPLORATORY OBJECTIVES: I. To correlate CD33 expression on AML cells with response to lintuzumab-Ac225 in combination with venetoclax and ASTX-727. II. To evaluate CD33 isoforms as a variable for response to lintuzumab-Ac225 combination with venetoclax and ASTX-727. OUTLINE: This is a dose-escalation study of lintuzumab-Ac225 in combination with venetoclax and ASTX-727. During dose-escalation phase, patients are randomized to 1 of 2 schedules. SCHEDULE 1: INDUCTION: Patients receive lintuzumab-Ac225 intravenously (IV) over 30 minutes on day 8, venetoclax orally (PO) once daily (QD) on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 1. RE-INDUCTION: Patients with CR, partial response (PR) or no response (NR) after cycle 1 receive lintuzumab-Ac225 IV over 30 minutes on day 8, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 2. MAINTENANCE/CONSOLIDATION: Patients with CRi, CRh, or morphologic leukemia-free state (MLFS) after cycle 1 receive venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study. SCHEDULE 2: INDUCTION: Patients receive lintuzumab-Ac225 V over 30 minutes on day 1, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 1. RE-INDUCTION: Patients with CR, PR or NR receive lintuzumab-Ac225 IV over 30 minutes on day 1, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 2. MAINTENANCE/CONSOLIDATION: Patients with CRi, CRh, or MLFS after cycle 1 receive venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
RADIATION	Actinium Ac 225 Lintuzumab	Given IV
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and biopsy
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and biopsy
DRUG	Decitabine and Cedazuridine	Given PO
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2026-04-21
• Primary completion: 2028-12-31
• Completion: 2028-12-31
• First posted: 2025-01-31
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study