A Diagnostic Study of CD38-Targeted ImmunoPET of Myeloma

Study Overview
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Brief Summary
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Evaluation of myeloma disease burden is currently suboptimal. This limits treatment planning and evaluation of residual disease following treatment. 89Zr-DFO-daratumumab is a novel immunoPET tracer, designed to detect CD38 on myeloma cells and allow visualization of myeloma in a PET scanner. A phase I study of 89Zr-DFO-daratumumab demonstrated safety and successful visualization of myeloma with 89Zr-DFO-daratumumab. This will be a phase II study of 89Zr-DFO-daratumumab to evaluate potential clinical applications of this novel imaging agent.

Detailed Description
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This will be a phase II clinical trial to assess the potential clinical value of 89Zr-DFO-daratumumab immunoPET. 60 patients with multiple myeloma (MM) and a plan for daratumumab containing combination therapy will be enrolled. Prior to therapy, current standard of care (SoC), as well as a research 89Zr-DFO-daratumumab PET/CT, tests will be performed. Patients will then undergo standard of care therapy for myeloma as defined by a medical oncologist and SoC response assessments as defined by the International Myeloma Working Group (IMWG). Upon suspected complete response (CR) or completion of 12 cycles of therapy, a repeat research 89Zr-DFO-daratumumab PET/CT will be repeated and standard of care minimal residual disease (MRD) assessment will be performed. This design will determine how 89Zr-DFO-daratumumab immunoPET compares with current methods of measuring and localizing disease prior to therapy, if immunoPET can predict response to therapy, and how immunoPET compares with current methods of detecting MRD after therapy. The therapy in this trial is standard of care. The research component is the addition of a novel immunoPET imaging test before and after standard of care therapy, to determine if the novel imaging test adds value over current measures of myeloma disease burden.

Official Title
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A Diagnostic Study of CD38-Targeted ImmunoPET of Myeloma: Phase 2 Trial of Clinical Applications

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: 89Zr-daratumumab PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 21 years of age Histologically/immunohistochemistry-confirmed CD38-positive multiple myeloma At least one tumor lesion on CT, MRI, or FDG PET/CT within 90 days of protocol enrollment ECOG performance status 0 to 2 Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study Exclusion Criteria: Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Life expectancy < 12 months Patients who cannot undergo PET/CT scanning because of weight limits. PET/CT scanners may not be able to function with patients over 450 pounds. History of anaphylactic reaction to humanized or human antibodies.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Sequential Assignment
Interventional Model Description: Individual dose of 89Zr-DFO-daratumumab will be requested from Memorial Sloan Kettering Cancer Center and received at the Hoag Family Cancer Institute radiopharmacy for each individual 89Zr-DFO-daratumumab administration.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD38-positive multiple myeloma<br>Patients with CD38 positive multiple myeloma with be enrolled. Patients will undergo pretreatment evaluation with standard of care diagnostic tests, as well as experimental 89Zr-daratumumab PET/CT. Patients will then undergo a course of standard of care therapy as defined by a medical oncologist. Following therapy, patients will repeat standard of care diagnostic tests, as well as experimental 89Zr-daratumumab PET/CT. Data analysis will be performed to evaluate 89Zr-daratumumab against standard of care diagnostic tests for the detection and localization of active disease before and after therapy. | Drug: 89Zr-daratumumab PET/CT<br>* CD38-targeting imaging<br>* Other names: CD38-targeted imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 89Zr-daratumumab PET/CT for pre-treatment multiple myeloma imaging | 89Zr-daratumumab PET/CT will be compared against standard of care laboratory and imaging measurements of multiple myeloma prior to therapy | up to 3 years | 
| 89Zr-daratumumab PET/CT for post-treatment multiple myeloma imaging | 89Zr-daratumumab PET/CT will be compared against standard of care laboratory and imaging measurements of multiple myeloma following therapy | up to 3 years | 
| Prediction of response to therapy | Determine if tumor uptake of 89Zr-daratumumab predicts response to therapy | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, 89Zr-daratumumab, Dartumumab, PET/CT