Trial Title:
PET Imaging Study of 68Ga-NB381 in Multiple Myeloma
NCT ID:
NCT06385652
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Fluorodeoxyglucose F18
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
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
Masking:
None (Open Label)
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:
Intervention type:
Drug
Intervention name:
68Ga-NB381
Description:
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.
Arm group label:
Head to head PET imaging comparison between 18F-FDG and 68Ga-NB381 for MM diagnosis
Other name:
18F-FDG
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking University First Hospital
Address:
City:
Beijing
Zip:
100000
Country:
China
Status:
Recruiting
Contact:
Last name:
Ronghui Yu, Master
Phone:
+8613466379791
Email:
kyc@bjmu.edu.cn
Investigator:
Last name:
Lei Kang, MD
Email:
Principal Investigator
Investigator:
Last name:
TIANYAO Wang, PhD
Email:
Principal Investigator
Investigator:
Last name:
Yongkang Qiu, Master
Email:
Sub-Investigator
Investigator:
Last name:
Zhenghao Tong, MD
Email:
Sub-Investigator
Start date:
April 1, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Peking University First Hospital
Agency class:
Other
Source:
Peking University First Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06385652
