NCT05363111

Radioimmunotherapy (111Indium/225Actinium-DOTA-daratumumab) for the Treatment of Relapsed/Refractory Multiple Myeloma

Phase 1 Trial of 111Indium/225Actinium-DOTA-Daratumumab in Patients With Relapsed/Refractory Multiple Myeloma

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of actinium Ac 225-DOTA-daratumumab (225Ac-DOTA-daratumumab) in combination with daratumumab and indium In 111-DOTA-daratumumab (111In-DOTA-daratumumab) in treating patients with multiple myeloma that does not respond to treatment (refractory) or that has come back (recurrent). Daratumumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. 111In-DOTA-daratumumab and 225Ac-DOTA-daratumumab are forms of radioimmunotherapy in which a monoclonal antibody, daratumumab, has been linked to a radiotracer to allow for targeted delivery of the treatment to cancer cells. Giving all three together may kill more cancer cells.

Detailed description

PRIMARY OBJECTIVE: I. To assess the safety and tolerability of 111In/225Ac-DOTA-daratumumab, at each dose level in order to establish the maximum tolerated dose (MTD), which will inform the recommended phase 2 dose (RP2D). SECONDARY OBJECTIVES: I. To describe the anti-myeloma activity of 225Ac-DOTA-daratumumab as assessed by overall response rate (ORR). II. To evaluate the organ biodistribution, pharmacokinetics and organ dose estimates of 111In/225Ac-DOTA-daratumumab. EXPLORATORY OBJECTIVE: I. To assess the activity of 225Ac-DOTA-daratumumab against non-cancer immune cells using the peripheral blood and bone marrow (BM) samples. OUTLINE: This is a dose-escalation trial of 225Ac-DOTA-daratumumab. Patients receive daratumumab intravenously (IV) over 45 minutes. Two hours later, patients receive 111In-DOTA-daratumumab and 225Ac-DOTA-daratumumab IV over 20-30 minutes. After completion of study treatment, patients are followed up weekly for 8 weeks, every 2 weeks for 4 weeks, every 4 weeks for 16 weeks, and then periodically up to 12 months.

Conditions

• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

Interventions

Type	Name	Description
BIOLOGICAL	Actinium Ac 225-DOTA-Daratumumab	Given IV
BIOLOGICAL	Daratumumab	Given IV
BIOLOGICAL	Indium In 111-DOTA-Daratumumab	Given IV

Timeline

• Start date: 2022-11-22
• Primary completion: 2027-03-23
• Completion: 2027-03-23
• First posted: 2022-05-05
• Last updated: 2025-10-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study