Central Nervous System Lymphoma

DALY II USA is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel (MB-CART2019.1) in patients with relapsed and/or refractory B cell lymphoma (BCL). Cohorts include subjects with diffuse large B-cell lymphoma (DLBCL) after receiving at least 2 lines of therapy, primary or secondary central nervous system (CNS) lymphoma (PCNSL) and (SCNSL) after receiving at least one line of therapy, mantle cell lymphoma (MCL) and Richter's transformation (RT) after receiving at least one line of therapy, and DLBCL transplant-ineligible after receiving at least one line of therapy.

The purpose of this clinical trial is to learn if drugs loncastuximab tesirine and rituximab (lonca-R) after stereotactic radiosurgery are safe and effective for treatment of central nervous system lymphomas.

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 phase I trial tests the safety, side effects, and best dose of intracerebroventricularly (ICV) administered CD19-chimeric antigen receptor (CAR) T cells in treating patients with central nervous system (CNS) lymphoma. CAR T cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein, CD19, on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. ICV is an injection technique that delivers the CD19-CAR T cells directly into the cerebrospinal fluid (which flows in and around the hollow spaces of the brain and spinal cord, and the thin layers of tissue that cover and protect the brain and spinal cord) in the brain, through a surgically placed catheter. Giving CD19-CAR T cells ICV may be more effective at treating patients with CNS lymphoma than giving them via other methods.

This research study is for people who have been diagnosed with large B-cell lymphoma of the central nervous system (CNS), which has either returned or is not responding to current treatment. Goldcadomide is a new experimental drug that works by binding to a specific protein inside cancer cells and helps stimulate immune cells that help fight cancer cells. It also has the ability to enter the central nervous system. It has shown promising safety and effectiveness when combined with standard of care chemotherapy. Participants will be treated with this study drug combined with standard of care chemotherapy. Participation in the research will last about 2.5 years. The purpose of this study is to help researchers learn if the study drug, Golcadomide, in combination with the standard of care regimen is a safe and effective way to treat large B-cell lymphoma with CNS involvement.

This study assesses neurocognitive outcomes after receiving radiation therapy to the brain (whole brain radiation therapy) in patients with blood cancers (hematologic malignancies). This may help researchers learn more about the effects of whole brain radiation therapy on memory and thinking in patients with blood cancer.

This is a Phase I/II, interventional, single-arm, open-label, treatment study designed to evaluate the safety and efficacy of Interleukin-7 and Interleukin-15 (IL-7/IL-15) manufactured chimeric antigen receptor (CAR)-20/19-T cells as well as the feasibility of a flexible manufacturing schema in adult patients with B cell malignancies that have failed prior therapies.

This is a prospective, single-Arm, phase II clinical study evaluating the efficacy and safety of thiotepa in combination with pirtobrutinib (a BTK Inhibitor) and sintilimab (a PD-1 Inhibitor) for frail or relapsed/refractory primary or secondary central nervous system lymphoma.It includes screening phase， induction therapy phase, and maintenance therapy phase.The screening period is defined as within 14 days prior to the first dose.Induction Treatment Phase: Enrolled subjects will receive a combination regimen of thiotepa, pirtobrutinib, and sintilimab. Treatment is administered in 21-day cycles for up to 6 cycles. Patients who achieve a disease response may proceed to consolidation therapy with either autologous hematopoietic stem cell transplantation or whole-brain radiotherapy at the investigator's discretion.Maintenance Treatment Phase: For patients who do not receive consolidation therapy with autologous transplantation or whole-brain radiotherapy, maintenance treatment with pirtobrutinib plus sintilimab will be initiated (for up to 1 year). Patients who receive any consolidation therapy will not proceed to maintenance treatment.Treatment response will be assessed throughout the study using the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria. The trial will monitor patient survival data, objective response rate (ORR), and safety parameters.Upon discontinuation of study treatment or completion of the 1-year treatment period, subjects will enter the follow-up phase. During follow-up, radiographic assessments (contrast-enhanced CT of the involved site is recommended) will be performed according to the following schedule: every 3 months for the first 2 years, every 6 months from Year 3 to Year 5, and annually after 5 years, until the end of the follow-up period. For subjects who have not withdrawn consent, survival information (including date and cause of death, subsequent anti-tumor therapies, etc.) will be collected every 3 months via telephone and/or clinical visit.

Subjects who met the inclusion/exclusion criteria were included in the experimental group after signing the informed consent form. One course of Z(R)-MTX(TMZ) treatment was given. After the results of the second-generation sequencing were reported, selinisol was added to the original treatment plan for those with TP53 mutations, and the original treatment plan was continued for those without TP53 mutations. Each course of treatment lasts for three weeks. A mid-term assessment is conducted after three courses of treatment, and a final assessment is carried out after six courses of treatment. After the mid-term or final assessment: If the PR is not achieved or the disease progresses at any time, the subjects are withdrawn from the group and receive salvage treatment. If the subjects achieve CR or PR, they enter maintenance treatment and continue with zanubrutinib for 2 years. For young patients (\< 65 years old), they can choose whether to receive ASCT as consolidation treatment according to their personal will, and then follow up and observe until 3 years have passed. SD/PD patients receive subsequent treatment after being judged by the researchers

This protocol is designed as a long-term follow-up study of participants who will receive CAR-T cells as part of a clinical trial at the Medical College of Wisconsin/ Froedtert Hospital. The clinical trials include the following: Phase 1 Study of CAR-20/19-T Cells in Patients with Relapsed Refractory B Cell Malignancies (NCT03019055); Phase I Trial of BCMA-TGF-BETA CAR-T Cells in Relapsed, Refractory Myeloma (NCT05976555); CAR20.19.22 T-cells in Relapsed, Refractory B-cell Malignancies (NCT05094206); LV20.19 CAR T-Cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies (NCT05990465); CAR-20/19-T Cells in Patients With Relapsed Refractory B Cell Malignancies (NCT04186520)

This is a single-arm and open-label study to explore X+MTX+Ritu (ATG-010, Methotrexate, Rituximab) regimen in Relapse refractory PCNSL patients. Approximately 30 patients will be enrolled in the study. In dose escalation phase, patients with Relapse refractory PCNSL will be treated with X+MTX+Ritu regimen and escalating doses of oral ATG-010 weekly in a 3+3 design. Then a phase 2 expansion at the recommended dose level based on phase 1b trial will be conducted to evaluate the efficacy, safety and tolerability.

This is an open-label, single-arm, phase I clinical trial with dose escalation designed to investigate the safety, tolerability, and pharmacokinetic properties of Human CD19-CD22 Targeted T Cells Infusion. The primary objectives are to preliminarily assess the impact of Human CD19-CD22 Targeted T Cells Infusion in patients with relapsed/refractory B-cell acute lymphoblastic leukemia and to explore the appropriate dose and reinfusion schedule for phase II. Eligible participants, including those with Central Nervous System Lymphoma, B Cell Lymphoma (BCL), Acute Lymphocytic Leukemia (ALL), Acute Lymphoblastic Leukemia (ALL), B Acute Lymphoblastic Leukemia (B-ALL), Refractory Non-Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia (CLL), Refractory B Acute Lymphoblastic Leukemia (B-ALL), Diffuse Large B Cell Lymphoma, Lymphoid Leukemia, and MRD-positive cases, can participate. Eligibility will be determined through a comprehensive assessment, including disease evaluations, a physical examination, Electrocardiograph, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and blood tests. Prior to the infusion of CD19-CD22 CAR+ T cells, participants will undergo chemotherapy. After the infusion, participants will be closely monitored for potential side effects and the effectiveness of CD19-CD22 CAR+ T cells. Certain study procedures may be conducted during hospitalization.

DALY II USA is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel (MB-CART2019.1) in patients with relapsed and/or refractory diffuse large B cell lymphoma (DLBCL) after receiving at least two lines of therapy. Additional cohorts include subjects with B-cell primary or secondary central nervous system (CNS) lymphoma (PCNSL) and (SCNSL), mantle cell lymphoma (MCL) and Richter's transformation (RT) after receiving at least one line of therapy.

This is a prospective single arm, phase II clinical trial to observe the efficacy and safety of orelabrutinib combined with pemetrexed in the treatment for patients with relapsed/refractory central nervous system lymphoma.

The objective of the observation is to collect and document data on treatment strategies for secondary central nervous system lymphoma (SCNSL) in routine clinical practice, whether obtained in the context of clinical trials or outside of trials. In particular, the following questions will be specified: * What therapeutic approaches are being pursued? * What is the clinical outcome of the various treatment options? * What is the frequency of serious adverse events with each therapeutic approach?

The study will include 28 patients with primary CNS DLBCL who are ineligible with autologous hematopoietic stem cell transplantation or whole brain radiation therapy as consolidation therapy. Induction treatment will include Rituximab and high dose methotrexate protocol (containing at least methotrexate and one more chemotherapy agent). Patients with MRI documented response CR or PR after induction chemotherapy will enter the study protocol of lenalidomide maintenance (at a dose of 15 mg per day, on days 1 to 21 of each 28-day cycle) for a maximum of 12 cycles, withdrew consent, the disease progressed, or unacceptable toxic effects occurred.