Primary Central Nervous System Lymphoma

The incidence of primary central nervous system lymphoma (PCNSL) has increased steadily, and the disease often progresses rapidly, with many patients presenting in critical condition. Timely biopsy and rapid pathological diagnosis are therefore essential for emergency management. However, biopsy is invasive and limited by bleeding risk, surgical contraindications, restricted tissue availability, and the effects of corticosteroid exposure or sampling location on pathological assessment. Moreover, delays inherent in imaging-based evaluation hinder the detection of very early relapse and may adversely affect patient outcomes. The investigators have focused on precision diagnosis and treatment of PCNSL, established an emergency-to-pathology rapid-response system and provided preliminary evidence from a small cohort that cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) has distinctive value for diagnosis and treatment-response assessment. A key biomarker-based panel achieved 100% specificity and 85% sensitivity. This project aims to establish a large, multicenter, disease-specific PCNSL database and characterize ctDNA alterations across more than 100 genes using ultra-deep sequencing. This project will integrate longitudinal CSF ctDNA profiles collected across disease stages with matched tissue-sequencing data. This approach will delineate the dynamic evolution of ctDNA molecular features and their spatiotemporal relationship with intratumoral heterogeneity. By developing multimodal AI models, the project aims to enable rapid early diagnosis, treatment-response prediction, and longitudinal disease monitoring, while elucidating mechanisms of therapeutic resistance and ultimately improving patient outcomes.

This randomized phase II trial studies how well obinutuzumab works as maintenance treatment in patients with central nervous system lymphoma who have achieved the disappearance of all signs of cancer in response to treatment (complete response) or a decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment (partial response). Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

This is a three-arm, multicenter, randomized controlled trial. Eligible participants will be randomized to one of three induction regimens via stratified block randomization at a 2:2:1 ratio. Induction regimens: Arm A: Teniposide + orelabrutinib + rituximab + methotrexate (MTX) + dexamethasone, administered in 21-day cycles. Arm B: Orelabrutinib + rituximab + MTX + dexamethasone, administered in 21-day cycles. Arm C: Rituximab + MTX + dexamethasone, administered in 21-day cycles. Participants achieving complete response (CR) or unconfirmed complete response (CRu) post-induction will proceed to consolidation therapy, with options including: MTX + rituximab (once every 3 months for 1 year); high-dose chemotherapy followed by autologous stem cell transplantation (ASCT); dose-reduced whole brain radiotherapy; or other modalities (as determined by the investigator).

This is a prospective, open-label, multicenter, randomized controlled study in treatment-naive patients with primary central nervous system lymphoma (PCNSL, DLBCL type). Eligible participants are randomized 1:1 to the experimental arm (R-MA-PD-1: rituximab, methotrexate, cytarabine plus penpulimab) or the control arm (R-MA: rituximab, methotrexate, cytarabine). Induction is administered every 21 days for 6 cycles, followed by risk- and response-adapted consolidation (ASCT or whole-brain radiotherapy) and penpulimab maintenance. The primary objective is to compare the 2-year progression-free survival rate between the two arms.

A double-blind, randomized phase II comparative trial will evaluate the superiority of the investigational treatment (tirabrutinib maintenance therapy) over standard care (observation with placebo) in terms of progression-free survival in patients with newly diagnosed primary central nervous system lymphoma (PCNSL) who have achieved complete response (CR or CRu) following induction therapy with high-dose methotrexate (HD-MTX)-based chemotherapy and have not undergone consolidative whole-brain irradiation. Participants will: Take protocol drug tirabrutinib or a placebo every day until disease progression or experience of unacceptable toxicity. Visit the clinic once every 4 weeks for checkups and tests, as well as protocol drug prescription.

This research study is studying a drug called Paxalisib (GDC-0084) as a possible treatment for primary central nervous system lymphoma (PCNSL)

The purpose of this study is to find out whether the combination of epcoritamab and ibrutinib is a safe treatment approach that causes few or mild side effects in people with relapsed/refractory primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL).

This is a single arm open-label multicenter phase I/II investigation of combination lenalidomide/Tafasitamab in patients with relapsed central nervous system (CNS) lymphoma. This is the first study to examine a naked anti-CD19 monoclonal antibody in relapsed CNS lymphoma patients as well as the combination of anti-CD19 antibody plus an Immunomodulatory imide drugs (IMiDs) in CNS lymphomas. This study will also test the novel hypothesis that Tafasitamab enhances blood-brain barrier permeability, a potential property that could have broad clinical implications.

The goal of this clinical trial is to evaluate the efficacy and safety of a four-drug combination regimen as first-line treatment for adults aged 18 years and older with newly diagnosed primary central nervous system lymphoma (PCNSL). The main questions it aims to answer are: Does the combination of pirtobrutinib, sintilimab, rituximab, and high-dose methotrexate achieve a higher complete response rate than standard treatment for newly diagnosed PCNSL? What is the safety and tolerability profile of this four-drug combination regimen? Researchers will compare the experimental four-drug combination to investigator-selected standard-of-care regimens (all based on high-dose methotrexate) to see if the experimental regimen improves complete response rate, progression-free survival, and overall survival while maintaining an acceptable safety profile. Participants will: Be assigned to either the experimental group or the standard treatment group based on their personal preference Receive 6 cycles of induction therapy (21 days per cycle) with their assigned treatment regimen Undergo regular clinical assessments, including contrast-enhanced brain MRI scans, blood tests, and cerebrospinal fluid examinations Complete the EORTC QLQ-C30 quality-of-life questionnaire at baseline, mid-treatment, end of treatment, and follow-up visits Receive optional consolidation or maintenance therapy based on their response to induction treatment Be followed for up to 2 years after completing treatment to monitor for disease progression and long-term outcomes

This study is being conducted to evaluate the safety and efficacy of the combination of pemetrexed and zanubrutinib (called induction therapy) followed by zanubrutinib treatment alone (also called maintenance therapy) in people who have relapsed or refractory (RR) primary central nervous system lymphoma (PCNSL) or isolated central nervous system relapse of B cell lymphoma (SCNSL). Assessments include how well people respond to this treatment, whether their disease gets better or worse, and their survival. Safety of this treatment and its side effects also will be assessed.

This research study is studying if the investigational drug, Pembrolizumab, in combination with chemotherapy helps primary central nervous system lymphoma with acceptable side effects. This research study involves a combination of the below drugs: * Pembrolizumab (a type of monoclonal antibody) * Methotrexate (a type of anti-metabolite) * Temozolomide (a type of alkylating agent) * Rituximab (a type of antibody)

This research study is evaluating a combination therapy of 3 drugs as possible treatments for recurrent primary central nervous system lymphoma (PCNSL). The three drugs being used in the study are: * Pembrolizumab (MK3475) * Ibrutinib * Rituximab (or biosimilar)

High-dose methotrexate (MTX) is the main componement of first line treatment in primary central nervous system lymphoma. Renal toxicity is the main dose limiting toxicity because of major MTX elimination by the kidneys. MTX crystallizes in renal tubules, leading to a renal failure (RF) and further delaying its elimination. When RF occurs, MTX accumulates, prolonging the duration of treatment exposure. MTX prolonging exposure can cause life-threatening complications and delay further treatments in the patient. Preventive measures have been developped, such as alkaline fluid hyperhydration and folic acid administration, to try to reduce the risk of these adverse events. In suspected severe RF in link to MTX is suspected, glucarpidase can be administared. However, this is an expensive treatment and not all patients recover normal renal function despite its use. MTX is an essential treatment for the management of PCNSL which is currently a curable disease especially in patients who are able to receive a consolidation treatment as thiotepa-based intensive consolidation followed by autologous stem cell transplantation (IC-ASCT). IC-ASCT requires a normal renal function, which could be impaired by severe RF secondary to MTX. The purpose of the study is to investigate how early dosing MTX could be used to simulate late concentrations. Early monitoring of MTX elimination could be implemented to identify patients at risk of delayed elimination and thus introduce rapid mesures as early administration of glucarpidase.

This phase I trial tests the safety, side effects, and best dose of Q702 in treating patients with hematologic malignancies. Q702 is in a class of medications called immunomodulatory agents. It works by helping the immune system kill cancer cells and by helping the bone marrow to produce normal blood cells. Giving Q702 may be safe, tolerable and/or effective in treating patients with hematologic malignancies.

This is a prospective single arm, multi-center, phase II clinical trial to observe the efficacy and safety of Rituximab, Lenalidomide combined with high-dose Methotrexate and Temozolomide (RL-MT) in the first-line treatment for patients with primary central nervous system lymphoma.

This study aims to observe and explore the efficacy and safety of Rituximab-Methotrexate-Temozolomide-Thiotepa (RMTT) regimen as first-line therapy for primary central nervous system diffuse large B-cell lymphomas(PCNS DLBCL)

Most patients being diagnosed with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) are 60 years or older. Elderly patients with PCNSL have a poor prognosis and there is a great medical need to improve outcome for this vulnerable population. In Germany and many international centres, there are currently two widely used strategies to treat elderly PCNSL patients who are eligible for high-dose methotrexate (HD-MTX) treatment, which have not yet been compared head-to-head. The R-MP regimen has been established by the Cooperative PCNSL Study Group as a "conventional" immunochemotherapy standard treatment for elderly patients with newly diagnosed disease and consists of Rituximab, HD-MTX and Procarbazine followed by maintenance therapy with Procarbazine. In contrast, another recently established protocol also includes HD-MTX-based induction therapy, but followed by consolidating high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT). This is an overall more intensive, but substantially shorter treatment approach, feasible for elderly patients being considered eligible for a more intensive treatment. The PRIMA-CNS trial aims to compare these two treatment approaches with respect to survival, response rates and toxicity.

This study is intend to improve the objective response rate in treatment of camrelizumab in recurrent primary central nervous system lymphoma patients.

It is a single arm, multicenter, phase 2 study to explore the efficacy and safety study of OR-MTX chemotherapy（Orelabrutinib, Rituximab and Methotrexate）as first-line regimens in the treatment of newly diagnosed primary central nervous system lymphoma. Objective response rate is the primary endpoint.

To explore PFS, ORR (CR/CRu+PR), OS and side effects of piamprizumab combined with RMA in newly diagnosed PCNSL, so as to clarify the value of piamprizumab combined with RMA in the first-line treatment of PCNSL patients, and to clarify the clinical and biological factors affecting the efficacy

This study suggests that R-IDARAM combined with intrathecal immunochemotherapy may be high effective in elderly patients with primary central nervous system lymphoma (PCNSL).

This study suggests that R-IDARAM combined with intrathecal immunochemotherapy may be high effective in primary central nervous system lymphoma (PCNSL) patients.