NCT06888323

Testing an Anti-cancer Radio-Active Immunotherapy Called Lintuzumab Ac225 in Patients With High-Risk Myelodysplastic Syndrome That Has Not Responded to Other Treatment

Lintuzumab-Ac225 Monotherapy for Patients With Hypomethylating Agent-Refractory Myelodysplastic Syndrome

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (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 for the treatment of patients with high risk myelodysplastic syndrome that has not responded to previous treatment (refractory). Lintuzumab-ac225 is a monoclonal antibody, called lintuzumab, linked to a radioactive agent called Ac225. Lintuzumab attaches to CD33 positive cancer cells in a targeted way and delivers Ac225 to kill them. Giving lintuzumab-ac225 may be safe, tolerable and/or effective in treating patients with high risk, refractory myelodysplastic syndrome.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety, tolerability, and maximum tolerated dose of actinium ac 225 lintuzumab (lintuzumab-ac225) monotherapy in myelodysplastic syndrome/neoplasm (MDS) patients whose disease is refractory to or progressing on hypomethylating agent (HMA) therapy. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To determine the efficacy, complete remission (CR) (CR/complete remission with incomplete bone marrow recovery \[CRi\]) rates, overall response rates (ORR), progression free survival (PFS), and overall survival (OS) of lintuzumab-Ac225 in MDS patients whose disease is refractory to or progressing on HMA therapy. III. To perform bulk ribonucleic acid (RNA) sequencing to assess transcriptomic changes in MDS patients after HMA therapy. IV. Dosimetry studies V. To study the correlation of absorbed radiation doses (in Gy) with adverse events and disease control. OUTLINE: This is a dose-escalation study of lintuzumab-ac225 followed by a dose-expansion study. Patients receive lintuzumab-ac225 intravenously (IV), over 30 minutes, on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo single photon emission computed tomography (SPECT)/CT scans and buccal swab on study, as well as bone marrow aspiration throughout the trial. After completion of study treatment, patients are followed for 90 days.

Conditions

• Refractory Myelodysplastic Syndrome

Interventions

Type	Name	Description
RADIATION	Actinium Ac 225 Lintuzumab	Given IV
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Buccal Swab	Undergo buccal swab
PROCEDURE	Computed Tomography	Undergo SPECT/CT
PROCEDURE	Single Photon Emission Computed Tomography	Undergo SPECT/CT

Timeline

• Start date: 2026-04-27
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2025-03-21
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study