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

NCT05363111 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 21599NCI-2022-03039P30CA033572
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs)

  Toxicity will be graded according to the National Cancer Institute (NCI)- Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  During the first 6 weeks post administration of study drug

• Maximum tolerated dose (MTD)

  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.

  During the first 6 weeks post administration of study drug

Secondary Outcomes (6)

• Overall response rate

  Up to 12 months

• Complete response rate

  Up to 12 months

• 12-month overall survival

  Time from first day of treatment to time of death due to any cause, assessed up to 12 months

• Progression free survival

  Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 12 months

• Time to progression

  Time from first day of treatment to the first observation of disease progression or death due to disease, assessed up to 12 months

Study Arms (1)

Treatment (daratumumab, 225Ac/111In-DOTA-daratumumab)

EXPERIMENTAL

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; Biological: Daratumumab; Biological: Indium In 111-DOTA-Daratumumab

Interventions

Actinium Ac 225-DOTA-Daratumumab BIOLOGICAL

Given IV

Also known as: 225Ac-DOTA-Daratumumab; [225Ac]-DOTA-Daratumumab

Treatment (daratumumab, 225Ac/111In-DOTA-daratumumab)

Daratumumab BIOLOGICAL

Given IV

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Treatment (daratumumab, 225Ac/111In-DOTA-daratumumab)

Indium In 111-DOTA-Daratumumab BIOLOGICAL

Given IV

Also known as: 111In-DOTA-Daratumumab; [111In]-DOTA-Daratumumab

Treatment (daratumumab, 225Ac/111In-DOTA-daratumumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Age \>= 18 years
• Karnofsky performance status (KPS) \> 60%
• Multiple myeloma according to International Myeloma Working Group (IMWG) criteria with measurable disease defined as one of the following:
• Serum monoclonal protein \>= 1.0 g/dL (or 0.5 g/dL in patients with immunoglobulin A \[IgA\] multiple myeloma \[MM\])
• hour urine monoclonal protein \>= 200 mg/24 hour
• Serum free light chain (FLC) of \> 10 mg/dL and an abnormal kappa:lambda ratio
• Minimum of two prior lines of therapy
• Previously received treatment with all of the following: a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Refractory (defined per IMWG Consensus Criteria) to daratumumab
• CD38 expression on multiple myeloma (MM) cells from bone marrow aspirate or biopsy as demonstrated by flow cytometry or immunohistochemistry
• Refractory (defined per IMWG Consensus Criteria) or intolerant to most recent therapy
• Fully recovered from the acute toxic effects (except alopecia) to =\< grade 1 to prior anti-cancer therapy
• Prior antitumor therapy must have been completed prior to enrollment as follows:
• \>= 21 days for investigational agents, cytotoxic chemotherapy

You may not qualify if:

• Daratumumab or other anti CD38 antibody treatment \< 3 months prior to study enrollment
• Prior radiopharmaceutical therapy
• Detectable antibodies directed against daratumumab
• Subject has received previous radiation to \> 25% of their bone marrow
• Female patients who are lactating or have a positive pregnancy test during the screening period
• Major surgery within 14 days prior to start of study treatment
• Subject is receiving concurrent chemotherapy, radiation, or biologic for cancer treatment. Subject is receiving bone marrow stimulatory factors (e.g., granulocyte-macrophage colony-stimulating factor \[GM-CSF\]). Note: Hormonal therapy for someone with a history of cancer treated with curative intent is permitted if subject has been on hormonal therapy \> 1 year
• Vaccination with live attenuated vaccines within 4 weeks of study agent administration
• A diagnosis of primary amyloidosis, plasma cell leukemia, Waldenstrom macroglobulinemia, or POEMS
• Severe persistent asthma (forced expiratory volume in 1 second \[FEV1\] \< 60% and/or daily symptoms) or severe chronic obstructive pulmonary disease (COPD) defined clinically or by historical pulmonary function tests with an FEV1 \< 50% predicted
• Subject has known allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or investigator's brochure). Patients with a history of infusion reactions to daratumumab with prior treatment that resolved with supportive measures and in whom daratumumab therapy was not previously discontinued because of infusion reactions are permitted
• Subject has uncontrolled human immunodeficiency virus (HIV-1), chronic or active hepatitis B, or active hepatitis A or C
• Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL or they have a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective antiretroviral therapy (ART) according to Department of Health and Human Services (DHHS) treatment guidelines is recommended
• Subject has any one of the following:
• Clinically significant abnormal electrocardiogram (ECG) finding at screening

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Indium

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Metals

Study Officials

• Scott R Goldsmith

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: May 5, 2022
• Study Start: November 22, 2022
• Primary Completion (Estimated): March 23, 2027
• Study Completion (Estimated): March 23, 2027
• Last Updated: October 29, 2025

Record last verified: 2025-10

Locations

US (1)