Registry of an Integrated Longitudinal Multimodal Biospecimen Biobank for Primary CNS Lymphoma in China

NCT07842835 | Recruiting DMC

• 1 other identifier: HX-C-2026006
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Primary Central Nervous System Lymphoma (PCNSL)

Keywords

Primary central nervous system lymphoma; Multimodal biobank; Prospective longitudinal cohort; Liquid biopsy; Circulating tumor DNA; Cell-free RNA; Multi-omics; Recurrence prediction

Outcome Measures

Primary Outcomes (6)

• Baseline data completeness rate

  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.

  At baseline, from enrollment through completion of baseline assessments（up to 30 months）

• Paired tumor tissue and cerebrospinal fluid sample acquisition rate

  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.

  within 1 month after biopsy or surgery (up to 30 months)

• Participant follow-up completion rate

  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.

  from enrollment to follow-up at Month 3, 6, 12, 24 and 36 (up to 36 months)

• Adherence to longitudinal cerebrospinal fluid sampling

  Percentage of scheduled cerebrospinal fluid collection visits completed among participants enrolled in the longitudinal cerebrospinal fluid/peripheral blood subcohort.

  Postoperative Month 1 and every 3-6 months thereafter (up to 36 months)

• Association between cerebrospinal fluid ctDNA clearance and MRI response

  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.

  3-6 months after pathological comfirmation (up to 36 months)

• Association of baseline and longitudinal ctDNA/cfRNA status with progression-free survival

  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.

  From the prespecified index date through Month 3, 6, 12, 24 and 36 (up to 36 months)

Secondary Outcomes (10)

• 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)

Study Arms (1)

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.

Drug: High-dose methotrexate-based therapy; Drug: Bruton tyrosine kinase inhibitor-based therapy

Interventions

High-dose methotrexate-based therapy DRUG

Standard-of-care treatment containing high-dose methotrexate as the backbone regimen, administered alone or in combination with other anticancer agents according to the treating physician's judgment and institutional practice. Treatment selection, dose, schedule, combination regimen, and duration are not assigned by the study protocol. Clinical response, recurrence, survival, adverse events, imaging findings, and longitudinal molecular biomarkers will be recorded prospectively.

PCNSL Cohort

Bruton tyrosine kinase inhibitor-based therapy DRUG

Standard-of-care treatment containing a Bruton tyrosine kinase inhibitor as a principal therapeutic component, administered alone or in combination with other anticancer agents according to the treating physician's judgment and institutional practice. The specific BTK inhibitor, dose, schedule, combination regimen, and duration are not assigned by the study protocol. Clinical response, recurrence, survival, adverse events, imaging findings, and longitudinal molecular biomarkers will be recorded prospectively.

PCNSL Cohort

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will be drawn from patients evaluated for suspected primary central nervous system lymphoma at participating tertiary referral hospitals in mainland China, including Beijing Tiantan Hospital, Shandong Provincial Hospital, and Tianjin Huanhu Hospital. Participants will be identified through departments of neurosurgery, hematology, neuro-oncology, radiology, and pathology. Healthy controls will be recruited from the participating institutions and surrounding communities to provide reference biospecimens and molecular profiles. The study will include a core PCNSL cohort, a non-PCNSL disease-control cohort, and a nested longitudinal cerebrospinal fluid/peripheral blood subcohort.

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Xiaohui Ren: lead
• Tianjin Huanhu Hospital: collaborator
• Shandong Provincial Hospital: collaborator

Study Sites (3)

Deparment of neurosurgery, Beijing tiantan hospital

Beijing, Beijing Municipality, 100070, China

RECRUITING

Deparment of neurosurgery, Shandong Provincial Hospital

Shandong, Jinan, 250021, China

RECRUITING

Deparment of neurosurgery, Tianjin huanhu hospital

Tianjin, Tianjin Municipality, 300222, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue obtained from diagnostic biopsy or surgical resection, cerebrospinal fluid, peripheral blood and derived plasma/serum, urine, saliva, and stool will be collected and retained. When available, tumor tissue will be stored as formalin-fixed paraffin-embedded and fresh-frozen specimens. Extracted DNA, RNA, circulating tumor DNA, and cell-free RNA, as well as other residual derivatives generated during approved multi-omics analyses, may also be retained for future research related to PCNSL diagnosis, molecular profiling, treatment-response monitoring, recurrence prediction, and prognosis.

Central Study Contacts

Xiaohui Ren, MD

CONTACT

+86-010-59975567; xiaohuiren@mail.ccmu.edu.cn/xiaohuiren@aliyun.com

Haoyi Li, MD

CONTACT

+86-010-59975567; lee_627269051@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Department of Neurosurgery, Beijing Tiantan Hospital

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: September 25, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): July 31, 2031
• Last Updated: September 30, 2026

Record last verified: 2026-09

Locations

CN (3)