Radioimmunotherapy (111Indium/225Actinium-DOTA-daratumumab) for the Treatment of Relapsed/Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT05363111|
Recruitment Status : Not yet recruiting
First Posted : May 5, 2022
Last Update Posted : July 27, 2022
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Biological: Actinium Ac 225-DOTA-Daratumumab Biological: Daratumumab Biological: Indium In 111-DOTA-Daratumumab||Phase 1|
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).
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Trial of 111Indium/225Actinium-DOTA-Daratumumab in Patients With Relapsed/Refractory Multiple Myeloma|
|Estimated Study Start Date :||September 30, 2022|
|Estimated Primary Completion Date :||April 9, 2025|
|Estimated Study Completion Date :||April 9, 2025|
Experimental: Treatment (daratumumab, 225Ac/111In-DOTA-daratumumab)
Patients receive daratumumab IV over 45 minutes. Two hours later, patients receive 111In-DOTA-daratumumab and 225Ac-DOTA-daratumumab IV over 20-30 minutes.
Biological: Actinium Ac 225-DOTA-Daratumumab
Other Name: 225Ac-DOTA-Daratumumab; [225Ac]-DOTA-Daratumumab
Biological: Indium In 111-DOTA-Daratumumab
Other Name: 111In-DOTA-Daratumumab; [111In]-DOTA-Daratumumab
- Incidence of dose-limiting toxicities (DLTs) [ Time Frame: During the first 6 weeks post administration of study drug ]Toxicity will be graded according to the National Cancer Institute (NCI)- Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Maximum tolerated dose (MTD) [ Time Frame: During the first 6 weeks post administration of study drug ]Toxicity will be graded according to the NCI-CTCAE version 5.0. The MTD is defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. The MTD will be based on the assessment of DLT during the first 6 weeks.
- Overall response rate [ Time Frame: Up to 12 months ]Will be defined as the proportion of patients meeting the criteria for partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR). Disease response will be evaluated per International Myeloma Working Group (IMWG) response criteria.
- Complete response rate [ Time Frame: Up to 12 months ]Will be defined as the proportion of patients meeting the criteria for CR or sCR.
- 12-month overall survival [ Time Frame: Time from first day of treatment to time of death due to any cause, assessed up to 12 months ]If a patient is still alive, survival time is censored at the time of last follow-up.
- Progression free survival [ Time Frame: Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 12 months ]If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up. Patients who start a new treatment regimen without documented progression will be censored.
- Time to progression [ Time Frame: Time from first day of treatment to the first observation of disease progression or death due to disease, assessed up to 12 months ]If failure has not occurred, failure time is censored at the time of last follow-up.
- Duration of response [ Time Frame: In patients with PR or better, time from first response documented until disease progression, assessed up to 12 months ]Deaths from causes other than progression will be censored and not included in calculation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05363111
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|Contact: Scott R. Goldsmith 626-218-3562 email@example.com|
|Principal Investigator: Scott R. Goldsmith|
|Principal Investigator:||Scott R Goldsmith||City of Hope Medical Center|