Clinical trial NCT06385652: PET Imaging Study of 68Ga-NB381 in Multiple Myeloma
Official title: Clinical PET Imaging Evaluation of 68Ga-NB381 Probe in Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2024-04-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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.
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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 80 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.

Primary outcomes:
measure: Specificity and Binding Efficiency of 68Ga-NB381 in CD38 Positive Tumors
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Lei Kang, MD
role: STUDY_DIRECTOR
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