About this trial
This phase I/II trial tests the safety and effectiveness of extramedullary disease (EMD)-directed external beam radiation therapy (EBRT) in combination with talquetamab for the treatment of multiple myeloma patients with extramedullary disease. Extramedullary disease in multiple myeloma involves the infiltration of organs and soft tissues by malignant plasma cells and has proven difficult to treat. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink cancers. EBRT is a type of radiation therapy that delivers high-energy beams to the cancer from outside of the body. In this trial, the EBRT will be directed to a site of extramedullary disease. Talquetamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Combining EMD-directed EBRT with talquetamab may be safe, tolerable, and/or effective in treating multiple myeloma patients with extramedullary disease.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
If unavailable, exceptions may be granted with study principal investigator (PI) approval
Disqualifiers
Prior irradiation to target EMD site or field
Prior GPRC5D therapy
Prior radiopharmaceutical therapy
Patients who have received previous radiation to > 25% of their bone marrow
Trial design
Single group
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Computed Tomography
Procedure/SurgeryUndergo CT and/or PET/CT
Electronic Health Record Review
Other interventionAncillary studies
External Beam Radiation Therapy
RadiationUndergo EMD-EBRT
Image Guided Biopsy
Procedure/SurgeryUndergo image-guided EMD biopsy
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Talquetamab
Biological/VaccineGiven SC
Treatment groups
Trial outcomes
Primary outcomes
Incidence of adverse events (phase 1b)
Toxicity will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome. Toxicity information recorded in each patient will include the type, severity, and the probable association with the study regimen. Tabular and graphical summaries will be used to represent the observed incidence by severity and type of toxicity.
Extramedullary disease (EMD)-modified overall response rate (ORR) (phase 2)
EMD-modified ORR 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 and Response Criteria for EMD. Clopper-Pearson 95% confidence intervals will be calculated for these estimates.
Secondary outcomes
Progression-free survival
Will be estimated using the product-limit method of Kaplan and Meier.
Overall survival
Will be estimated using the product-limit method of Kaplan and Meier.
Duration of response
Will be evaluated in patients with PR or better. Will be estimated using the product-limit method of Kaplan and Meier.
Clinical benefit rate
Clinical benefit rate will be defined as the proportion of patients meeting the criteria for stable disease, PR, VGPR, CR, or sCR. Disease response will be evaluated per IMWG response criteria. Clopper-Pearson 95% confidence intervals will be calculated for these estimates.
Sponsors and contacts
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator