Multiple Myeloma
Conditions
Brief summary
Multiple myeloma (MM) predominantly affects the elderly, often presenting insidiously and with a rising incidence rate. Current diagnostic methods primarily rely on invasive bone marrow biopsies, which can lead to false-negative results if the biopsy site is improperly chosen. CD38 is significantly overexpressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker for this disease. Addressing the limitations in specificity and sensitivity of traditional PET imaging agents, this project is dedicated to developing a new type of nanobody PET/CT imaging probe, 68Ga-NB381, which possesses high affinity and targets CD38. This probe, which is an intellectual property of our institution, aims to enhance the accuracy and specificity of early MM diagnosis. In terms of clinical evaluation, the project will implement a comprehensive assessment process including case selection, collection of baseline information, high-precision imaging, expert-level image interpretation, and follow-up studies, comparing directly with traditional 18F-FDG imaging to thoroughly verify the specificity and safety of 68Ga-NB381. This lays the groundwork for the clinical translation of this radiopharmaceutical in China. Furthermore, the project contributes to formulating more effective precision treatment plans based on CD38 expression levels and provides evidence for monitoring the therapeutic effects of daratumumab, a drug also targeting CD38. This makes the project of significant academic value and clinical importance, thus promoting the development of personalized treatment strategies.
Detailed description
Multiple myeloma (MM) commonly occurs in the elderly and often remains undetected until it reaches an advanced stage. With the aging population in China, the incidence of MM is on the rise, now surpassing that of acute leukemia. Clinically, MM is characterized by bone destruction and lacks specificity; diagnosis primarily relies on bone marrow biopsies that detect an increase in clonal plasma cells, which are invasive and can yield false-negative results if the biopsy site is improperly selected. CD38 is significantly overexpressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker for MM. As the incidence of malignant tumors in China continues to increase, so does the clinical demand for radiopharmaceuticals. Addressing the limitations in the targeting of 18F-FDG in PET imaging, the development of new targeted nuclear medicine molecular probes is of significant academic value and clinical importance, particularly in monitoring the therapeutic effects of the CD38-targeted nanobody NB381, which offers unique advantages. This project uses a nanobody with high affinity for CD38 as the targeting moiety for the radiopharmaceutical, exploring the diagnostic efficiency of 68Ga-NB381 in patients with MM exhibiting high CD38 expression. This not only provides a basis for the early diagnosis of MM but also allows for the formulation of effective precision treatment strategies based on the CD38 expression profile in MM patients. 68Ga-NB381, a new CD38-targeted molecular probe labeled with 68Ga, can be used for the diagnosis and research of various malignancies expressing high levels of CD38, including MM. The probe is conjugated with 68Ga3+ using TOHP as a bifunctional chelator, with a simple labeling process that does not require purification, offering high in-vivo stability and significant radioactive accumulation in tumor sites in mouse models, resulting in superior imaging outcomes. This project will complete the automation of the 68Ga-NB381 labeling process and conduct quality control studies on the resulting radiopharmaceutical injection solution, establishing quality standards for this new PET probe and laying the foundation for its clinical translation in China. The project aims to provide 68Ga-NB381 PET/CT imaging studies to support the early diagnosis of CD38 high-expression malignancies, the formulation of treatment plans, and the assessment of therapeutic efficacy.
Interventions
DRUG68Ga-NB381
Lei Kang from Peking University First Hospital and Bing Jia's team from the School of Basic Medical Sciences at Peking University have developed a targeted CD38 nanobody sequence using genetic engineering technology. They have optimized its structure, functionalized it with labeling, and conducted imaging and other evaluations, ultimately producing the CD38-targeted nuclear medicine small molecule diagnostic and therapeutic agent-68Ga-labeled nanobody NB381. The post-labeling quality control of the drug meets clinical trial requirements with a radiochemical purity (PCR) greater than 98% and in vitro stability not less than 90%. Preliminary PET imaging results of 68Ga-NB381 indicate that the nanobody is primarily concentrated in the kidneys, bladder, and MM.1S and Ramos or H929 tumors (CD38+). Additionally, the cold antibody NB381 significantly inhibits the uptake of 68Ga-NB381 in tumors, confirming the high specificity of this nanobody's binding to the CD38 protein.
Sponsors
Peking University First Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Masking description
All PET/CT images are jointly interpreted by at least two imaging and nuclear medicine physicians, each with several years of diagnostic experience and at least at the attending physician level. They compare and record the number of lesions detected and the SUVs (Standard Uptake Values) for both 18F-FDG and 68Ga-NB381 PET/CT scans. After consultation, they provide a unified diagnostic opinion.
Intervention model description
In this sequential assignment clinical trial, we aim to evaluate and compare the diagnostic performance of two PET imaging agents, 68Ga-NB381 and 18F-FDG, in patients diagnosed with multiple myeloma (MM). The study will enroll MM patients who meet the inclusion criteria and are scheduled for routine diagnostic imaging. Each participant will undergo PET imaging with 18F-FDG first, followed by a second PET scan using 68Ga-NB381 (or reversed). To minimize potential interference between the two imaging sessions and ensure patient safety, a minimum interval of one day will be maintained between the two scans, with all imaging completed within one week. This sequential imaging approach allows for direct comparison of the imaging agents in the same patient, thus controlling for inter-patient variability and providing a more accurate assessment of the relative merits of each imaging agent in the same metabolic and pathological condition.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Patients suspected of multiple myeloma who are scheduled to undergo bone marrow aspiration or tissue biopsy within the next 3 months; aged between 18 and 90 years; participants must fully understand and voluntarily participate in this study, and sign an informed consent form; must be able to independently comply with the examination procedures. * Confirmed symptomatic multiple myeloma patients; aged over 18 years; participants must fully understand and voluntarily participate in this study, and sign an informed consent form; must be able to independently comply with the examination procedures.
Exclusion criteria
* Pregnant women * Individuals who cannot understand the examination process or are unable to cooperate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Specificity and Binding Efficiency of 68Ga-NB381 in CD38 Positive Tumors | For a single patient, imaging and analysis will be conducted within 24 hours post-injection; follow-up assessments for stability and biodistribution will be conducted at 1 week post-injection. | Evaluate the specificity and binding efficiency of 68Ga-labeled NB381 nanobody in targeting CD38 positive tumors using PET imaging. The measure involves comparing the uptake of 68Ga-NB381 in CD38 positive tumors to non-target areas and assessing the ability of cold antibody NB381 to inhibit this uptake, thus confirming the high specificity of the nanobody for CD38 protein. |
| Baseline Pathological Characteristics: Histopathology, Flow Cytometry, and Immunohistochemistry | Baseline (within 28 days prior to first dose of study intervention) | Baseline bone marrow pathological assessments will be performed, including: (1) histopathological evaluation of plasma cell infiltration; (2) flow cytometry to quantify the proportion of malignant plasma cells and CD38-positive cells; and (3) immunohistochemical profiling for relevant markers (e.g., CD138, κ/λ light chain restriction). Results will be summarized descriptively for baseline disease characterization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Disease Characterization: International Staging System (ISS) Stage and Immunofixation Electrophoresis (IFE) Type | Baseline (within 28 days prior to first dose of study intervention) | Baseline disease characteristics of enrolled participants will be documented, including: (1) International Staging System (ISS) stage (I, II, or III), determined by serum β2-microglobulin and albumin levels per International Myeloma Working Group (IMWG) criteria; and (2) Immunofixation electrophoresis (IFE) type identifying the monoclonal protein isotype (e.g., IgG κ, IgG λ, IgA κ, IgA λ, IgD, free light chain-only, or non-secretory disease). These baseline stratification factors will be summarized descriptively and may be used for pre-specified subgroup analyses to evaluate treatment effect consistency across disease risk profiles. |
| Baseline Laboratory Assessments: Hematology, Clinical Chemistry, and Myeloma-Specific Biomarkers | Baseline (within 28 days prior to first dose of study intervention) | Baseline laboratory parameters will be collected, including complete blood count, clinical chemistry (renal/hepatic function, electrolytes, LDH), serum immunoglobulins, serum and urine M-protein quantification, serum free light chains with κ/λ ratio, and urine immunofixation electrophoresis. Results will be summarized descriptively and may be used for baseline characterization and subgroup analyses. |
| Treatment Response Assessment per IMWG Criteria | End of Cycle 2 (approximately 2 months after first dose) and End of Cycle 4 (approximately 4 months after first dose) | Treatment response will be evaluated according to the International Myeloma Working Group (IMWG) consensus criteria, categorizing disease status as stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD), or progressive disease (PD). Results will be used to assess preliminary antitumor efficacy. |
Countries
China
Contacts
CONTACTTIANYAO Wang, PhD
CONTACTLei Kang, MD
STUDY_DIRECTORLei Kang, MD
Peking University First Hospital
Outcome results
None listed