Registry of an Integrated Longitudinal Multimodal Biospecimen Biobank for Primary Central Nervous System Lymphoma in China（CLIMB）
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 400
- 试验地点
- 3
- 主要终点
- Baseline data completeness rate
研究概览
简要总结
This project aims to establish and prospectively register a longitudinal, multimodal biobank for primary central nervous system lymphoma (PCNSL). The study will primarily enroll patients undergoing needle biopsy or surgical resection of lesions involving the brain, spinal cord, or meninges, with a pathological diagnosis of central nervous system lymphoma. To ensure population homogeneity, patients with PCNSL will constitute the core analysis cohort. Patients with imaging findings suggestive of PCNSL but a final pathological diagnosis other than PCNSL will serve as disease controls, and matched healthy volunteers will be recruited as baseline controls.
At baseline, biopsy tissue, cerebrospinal fluid (CSF), peripheral blood, urine, saliva, and stool samples will be collected. Follow-up visits will be scheduled at 1 month after biopsy and every 3-6 months thereafter, with contrast-enhanced brain magnetic resonance imaging (MRI) and serial collection of CSF and peripheral blood. After the requirements of routine pathological diagnosis have been met, biopsy specimens will undergo tiered multi-omics profiling according to sample availability and freshness, including whole-exome sequencing, bulk RNA sequencing, single-cell RNA sequencing, metabolomics, spatial transcriptomics, and spatial metabolomics. Analyses of CSF and blood samples will focus on circulating tumor DNA and cell-free RNA (ctDNA/cfRNA), supplemented by conventional cytology, flow cytometry, and other clinical data for longitudinal disease monitoring.
The project will develop an integrated database incorporating clinical, imaging, pathological, molecular, and biospecimen data. It will characterize the relationships of baseline tissue multi-omics features and longitudinal changes in CSF- and blood-derived ctDNA/cfRNA with treatment response, recurrence prediction, and prognosis. The study will also develop diagnostic and risk-stratification models applicable to patients at our institution, across the region, and potentially throughout mainland China, while establishing standardized operating procedures for biospecimen collection and processing. This work is expected to provide high-quality evidence and a sustainable translational research platform for elucidating the biological heterogeneity of PCNSL, validating liquid-biopsy biomarkers, and optimizing precision follow-up strategies.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General Criteria for Patient Participants Age ≥18 years. Radiological findings suspicious for primary central nervous system lymphoma (PCNSL).
- •Scheduled to undergo needle biopsy or surgical resection of a lesion involving the brain, spinal cord, or meninges.
- •Willing and able to provide written informed consent.
- •Core PCNSL Cohort
- •Patient participants must additionally meet all of the following criteria:
- •Histopathologically confirmed PCNSL. Able and willing to comply with scheduled study follow-up. Able to undergo magnetic resonance imaging examinations. Non-PCNSL Disease Control Cohort
- •Patient participants must meet the following criterion:
- •Initially suspected of having PCNSL based on imaging findings but ultimately diagnosed with a condition other than PCNSL by histopathological examination.
- •Healthy Control Cohort Age ≥18 years. Eligible for recruitment as a healthy control according to the study screening procedures.
- •Meets the prespecified matching requirements for the study cohorts. Willing and able to provide written informed consent. Additional Criteria for the Longitudinal CSF/Peripheral Blood Subcohort
- •Participants entering this subcohort must additionally meet all of the following criteria:
- •No contraindication to lumbar puncture, as determined by the study physician. Willing and able to undergo serial cerebrospinal fluid and peripheral blood collection.
- •Provides separate explicit informed consent for longitudinal biospecimen collection.
- •Final eligibility for all cohorts will be determined by the study investigator based on the participant's clinical condition, pathological findings, and relevant examination results.
排除标准
- •Exclusion Criteria for Patient Cohorts PCNSL is suspected based on imaging findings, but no definitive histopathological diagnosis can be obtained.
- •Estimated life expectancy of less than 3 months and, in the investigator's judgment, inability to complete the minimum required clinical data or biospecimen collection.
- •Refusal to provide written informed consent or withdrawal of informed consent.
- •Additional Exclusion Criteria for the Longitudinal CSF/Peripheral Blood Subcohort
- •Participants will be excluded from research lumbar puncture if any of the following conditions are present:
- •Severe coagulation disorder. Marked or severe intracranial hypertension. Evidence of, or substantial risk for, cerebral herniation. Spinal infection or central nervous system infection. Any other definite contraindication to lumbar puncture, as determined by the investigator.
- •Exclusion Criteria for Healthy Controls Presence of a severe systemic disease. Any condition that, in the investigator's judgment, makes the individual unsuitable for participation.
- •Refusal to provide written informed consent or withdrawal of informed consent.
研究组 & 干预措施
PCNSL Cohort
Adults with pathologically confirmed primary central nervous system lymphoma (PCNSL) following biopsy or surgical resection of a brain, spinal cord, or meningeal lesion. Clinical, imaging, pathological, treatment, and outcome data will be collected. Tumor tissue, cerebrospinal fluid, peripheral blood, urine, saliva, and stool will be collected at baseline, as available. Eligible consenting participants without contraindications to lumbar puncture may enter a longitudinal biospecimen subcohort, with contrast-enhanced brain MRI and serial cerebrospinal fluid and peripheral blood collection at postoperative Month 1 and every 3-6 months thereafter.
干预措施: High-dose methotrexate-based therapy (Drug)
PCNSL Cohort
Adults with pathologically confirmed primary central nervous system lymphoma (PCNSL) following biopsy or surgical resection of a brain, spinal cord, or meningeal lesion. Clinical, imaging, pathological, treatment, and outcome data will be collected. Tumor tissue, cerebrospinal fluid, peripheral blood, urine, saliva, and stool will be collected at baseline, as available. Eligible consenting participants without contraindications to lumbar puncture may enter a longitudinal biospecimen subcohort, with contrast-enhanced brain MRI and serial cerebrospinal fluid and peripheral blood collection at postoperative Month 1 and every 3-6 months thereafter.
干预措施: Bruton tyrosine kinase inhibitor-based therapy (Drug)
结局指标
主要结局
Baseline data completeness rate
时间窗: At baseline, from enrollment through completion of baseline assessments（up to 30 months）
Percentage of enrolled participants with complete required baseline clinical, imaging, pathological, treatment, and biospecimen information in the electronic case report form. The numerator is the number of participants with all protocol-required baseline data; the denominator is the total number of enrolled participants.
Paired tumor tissue and cerebrospinal fluid sample acquisition rate
时间窗: within 1 month after biopsy or surgery (up to 30 months)
Percentage of eligible participants from whom both evaluable tumor tissue and cerebrospinal fluid samples are successfully collected and stored according to the study standard operating procedures.
Participant follow-up completion rate
时间窗: from enrollment to follow-up at Month 3, 6, 12, 24 and 36 (up to 36 months)
Percentage of enrolled participants who complete the protocol-required clinical and imaging follow-up assessments at Month 12 and Month 24. Completion rates will be calculated separately for each time point.
Adherence to longitudinal cerebrospinal fluid sampling
时间窗: Postoperative Month 1 and every 3-6 months thereafter (up to 36 months)
Percentage of scheduled cerebrospinal fluid collection visits completed among participants enrolled in the longitudinal cerebrospinal fluid/peripheral blood subcohort.
Association between cerebrospinal fluid ctDNA clearance and MRI response
时间窗: 3-6 months after pathological comfirmation (up to 36 months)
Cerebrospinal fluid circulating tumor DNA status will be classified as cleared or not cleared at postoperative Month 3 and compared with concurrent MRI response categories-complete response, partial response, stable disease, or progressive disease. The association or agreement will be assessed using contingency-table analysis, kappa statistics, and/or receiver operating characteristic analysis, as applicable.
Association of baseline and longitudinal ctDNA/cfRNA status with progression-free survival
时间窗: From the prespecified index date through Month 3, 6, 12, 24 and 36 (up to 36 months)
Progression-free survival will be evaluated according to baseline and longitudinal cerebrospinal fluid or peripheral blood ctDNA/cfRNA status. Progression-free survival is the time from the prespecified index date to radiographic or clinical disease progression or death from any cause, whichever occurs first.
次要结局
- Objective response rate(From treatment initiation to follow-up at month 3,6,12,24 and 36 (up to 36 months))
- Best overall response(From treatment initiation to follow-up at month 3,6,12,24 and 36 (up to 36 months))
- Progression-free survival(From treatment initiation to follow-up at month 3,6,12,24 and 36 (up to 36 months))
- Overall survival(From treatment initiation to follow-up at month 3,6,12,24 and 36 (up to 36 months))
- Lead time from molecular recurrence detected by cerebrospinal fluid ctDNA to radiographic recurrence(Postoperative Month 1 and every 3 months thereafter (up to 36 months))
- Concordance and clinical associations of key driver variants in tumor tissue and cerebrospinal fluid(At baseline and every 3-6 months after pathological confirmation （up to 36 months）)
- Molecular evolution between diagnosis and recurrence(From baseline to the first documented recurrence (up to 36 months))
- Change in neurological and performance status(At baseline and every 3-6 months thereafter (up to 60 months))
- Change in cognitive function(At baseline and every 3 months thereafter (up to 60 months))
- Incidence of treatment-related adverse events(From enrollment to follow-up (up to 36 months))
研究者
Xiaohui Ren
Department of Neurosurgery, Beijing Tiantan Hospital
Beijing Tiantan Hospital