Diffuse Large B-Cell Lymphoma

Researchers are evaluating a new type of CAR T cell therapy called 4SCAR19U T cells for treating patients with CD19-positive B cell malignancies. This phase I trial aims to assess the feasibility, safety, and effectiveness of this universal CAR T cell product in patients who have relapsed or refractory hematological cancers. The study also investigates how these cells function and persist in the body. The trial is sponsored by Shenzhen Geno-Immune Medical Institute and conducted at multiple centers. The 4SCAR19U T cells are genetically engineered and produced in large amounts, allowing them to be stored and used off-the-shelf without needing to be custom-made for each patient. This makes treatment quicker and potentially more accessible, especially for patients with rapidly progressing disease or weakened immune systems after chemotherapy or radiotherapy. Participants will receive infusions of these universal CD19-specific CAR T cells as the investigational therapy. Participants will be monitored for safety over 24 weeks following the infusion to observe any side effects or adverse events. The study will also evaluate the anti-tumor activity of the 4SCAR19U cells for up to one year. Assessments include clinical evaluations, laboratory tests, and tracking of the cells persistence in the body. The trial plans to enroll patients aged from 6 months to 75 years, with specific health and response criteria, and participation could last until the studys end date in 2030.

Researchers are studying the use of 90YY-PentixaTher 90YY-PTT to treat patients with recurrent or refractory primary or isolated secondary central nervous system CNS lymphoma. This open-label, single-arm phase 12 study aims to evaluate the safety, tolerability, biodistribution, and preliminary effectiveness of this treatment. The study includes three dose-level groups, and a safety review committee will carefully monitor for any dose-limiting side effects to guide dose adjustments. Participants will receive one cycle of 90YY-PTT administered intravenously. The study follows a best-of-5 dose escalation design across three cohorts with different dose levels. There is no comparison group in this study. After the treatment, patients will undergo several visits during the core study phase to assess safety, how the drug spreads in the body, dosimetry, and treatment response. Following this, three follow-up visits will occur at three-month intervals to monitor disease status. Throughout the study, participants will be closely monitored for adverse events, with severity graded by standard criteria. Various imaging and laboratory tests will be performed shortly after infusion and at multiple time points to measure drug uptake in tumors and organs, blood levels, and absorbed radiation doses. Researchers will assess response rates, progression-free survival, and overall survival at one, three, six, nine, and twelve months after treatment. The total study duration includes screening, treatment, core evaluations, and extended follow-up visits to comprehensively evaluate treatment outcomes and safety.

Researchers are evaluating CT1182, an in vivo CAR-T cell therapy, in patients with relapsed or refractory B-cell Non Hodgkin Lymphoma rr B-NHL. This early phase 1, open-label study aims to explore the safety, effectiveness, metabolic behavior, and pharmacodynamics of CT1182 cells. The study intends to identify the maximum tolerated dose MTD by testing four dose levels, with a target toxicity probability of 30%, to understand how the treatment affects patients with various subtypes of B-NHL. Participants will receive intravenous infusions of CT1182 at escalating dose levels ranging from 1.2 108 to 1.2 109 TU. The dose escalation follows a Bayesian Optimal Interval design, with safety monitored over a 28-day dose-limiting toxicity DLT observation period after the first infusion. If no DLT is observed, doses may be adjusted if ineffective expansion of CAR-T cells is detected, early withdrawal or continued safety observation is possible. The study plans to enroll between 3 and 24 participants, with dosing and cohort size adjusted according to ongoing results. During the study, participants will be closely monitored for adverse events, DLTs, and response rates for up to 24 months after infusion. Evaluations include clinical assessments, laboratory tests, and measurement of CAR gene copy numbers at multiple timepoints. Outcome measures include safety profiles, objective and complete response rates, duration and time to remission, progression-free survival, overall survival, and metabolic kinetics of the lentiviral vectors used in treatment. The study follows participants through long-term safety and efficacy assessments to better understand CT1182s impact.

Researchers are evaluating the safety and effectiveness of an investigational treatment called RN1101, which are allogeneic CAR-T cells targeting CD19 and BCMA. This early-phase, open-label pilot study focuses on patients with relapsed or refractory B-cell or plasma cell-derived malignant tumors, including B-cell lymphoma and multiple myeloma. The study plans to enroll 21 patients to understand how well this treatment works and its safety profile for these challenging cancers. Participants will receive a single intravenous infusion of RN1101 cells designed to target and attack cancerous B cells or plasma cells. The study involves a dose-escalation approach where all patients receive the experimental therapy. Researchers will monitor the treatments ability to reduce or eliminate cancer cells expressing CD19 or BCMA and evaluate how long these CAR-T cells persist in the body. Throughout the study, participants will be closely followed for up to 24 weeks after the infusion. Researchers will assess safety by tracking adverse events and measure effectiveness using outcomes such as minimal residual disease status, response rates, progression-free survival, overall survival, and CAR-T cell presence in blood and bone marrow. Blood tests, imaging, and clinical evaluations will be performed regularly to monitor treatment response and participant health over this period.

Researchers are evaluating MK-1045, an immunotherapy, in people with two types of non-Hodgkin lymphoma NHL follicular lymphoma FL, which grows slowly, and diffuse large B-cell lymphoma DLBCL, which grows more quickly. NHL is a cancer of the lymphatic system causing swollen lymph nodes. This study aims to assess the safety and tolerability of MK-1045 and to see if it can shrink or eliminate these lymphomas. Participants are randomly assigned to one of four groups receiving different doses or methods of MK-1045 administration. Dosages A, B, and D are given by intravenous IV infusion, while Dosage C is given by subcutaneous SC injection. Treatment lasts for up to approximately one year or until participants stop treatment for any reason. During the study, participants will be monitored for adverse events and treatment side effects, with measurements including tumor response using specific criteria. Blood levels of MK-1045 will also be tracked. The study involves regular visits for infusions and assessments. Participant safety and treatment effects will be followed for up to about 49 months in total.

Researchers are evaluating treatments for germinal center B-cell-like diffuse large B-cell lymphoma GCB DLBCL, a fast-growing blood cancer affecting immature B-cells. The study compares two treatment combinations to see if more people respond to zilovertamab vedotin MK-2140 plus R-CHP versus polatuzumab vedotin plus R-CHP. This Phase 2 trial aims to assess the effectiveness and safety of these regimens in participants with newly diagnosed GCB DLBCL. Participants receive either zilovertamab vedotin along with rituximab, cyclophosphamide, doxorubicin, and prednisone R-CHP, or polatuzumab vedotin combined with R-CHP. Treatments are given by intravenous infusion on Day 1 of each 3-week cycle for up to 6 cycles, approximately 4 months, with prednisone or prednisolone taken orally for 5 days of each cycle. For participants with high-risk DLBCL, up to 2 additional cycles of rituximab or biosimilar are given. During the study, participants are monitored for response to treatment using Lugano Response Criteria, with follow-up lasting up to about 31 months for the primary outcome. Secondary outcomes include progression-free survival, overall survival, event-free survival, duration of complete response, adverse events, and quality of life assessments. Safety and health status are regularly checked through exams, lab tests, and questionnaires over several years, with total study participation extending up to 7 years.

Researchers are evaluating the efficacy and safety of TQB3702 tablets combined with immunochemotherapy for treating B-cell lymphoma. This Phase II clinical trial focuses on patients diagnosed with specific types of B-cell lymphoma, including relapsed or refractory indolent B-cell lymphoma and diffuse large B-cell lymphoma DLBCL. The study aims to assess how well this combination therapy works and its overall safety. Participants will receive TQB3702 tablets at a dose of 200 mg every 4 weeks as one treatment cycle. Alongside this, they will undergo chemotherapy cycles every 3 or 4 weeks, with a total of 6 to 12 cycles of combination therapy. The chemotherapy regimen is designed to inhibit tumor cell growth, suppress DNA synthesis, induce cancer cell death, support immune function, and prevent new blood vessel formation that supports tumors. During the trial, participants will be closely monitored for treatment response and safety. Researchers will measure overall and complete response rates up to 2 years, as well as adverse events, progression-free survival, duration of response, and overall survival up to death from any cause. The study includes assessments from baseline through combination therapy completion and follow-up periods lasting up to 2 years. This comprehensive monitoring helps understand both the immediate and longer-term effects of the treatment.

Researchers are evaluating the safety and activity of ADX-2191 methotrexate injection USP given directly into the eye for patients with primary vitreoretinal lymphoma. This Phase 3, multicenter, randomized, double-masked clinical trial compares different dosing schedules to understand how well they clear lymphoma cells from the eye. Participants will receive one of two treatment methods after developing lymphomatous vitreous cells in at least one eye. One group will follow the InductionConsolidationMaintenance ICM dosing of ADX-2191, receiving intravitreal injections twice weekly for four weeks, then weekly for eight weeks, totaling sixteen injections. The other group will receive monthly ADX-2191 injections for three months, with sham injections during other visits for a total of thirteen sham injections. During the study, participants will be monitored for the clearance of lymphoma cells in the eye over eight weeks. The main measure is the proportion of patients whose vitreous cells clear after treatment. Safety and response will be assessed through regular visits and evaluations. The trial will continue until December 2026, with all study-related care provided under careful observation.

Researchers are evaluating ONM-501, a drug given as intratumoral injections, alone and in combination with cemiplimab, an immune checkpoint inhibitor, in patients with advanced solid tumors and lymphomas. This phase 1 study aims to find the maximum tolerated dose, minimum effective dose, and recommended dose for expansion of ONM-501. The study includes patients with various advanced cancers who have no alternative standard therapies available. The trial has three parts monotherapy dose escalation, combination therapy dose finding, and combination therapy dose expansion. ONM-501 is given once per week for three weeks followed by three weeks off, in 21-day cycles. Cemiplimab is given intravenously every three weeks during the combination phases. Dose escalation uses special methods to gradually increase doses, and after doses are established, patients will enroll in expansion cohorts for specific tumor types. Participants will have regular assessments including monitoring for side effects, blood tests to measure drug levels, and evaluation of tumor response over up to 24 months. Researchers will track treatment-emergent adverse events, dose-limiting toxicities, and serious adverse events. Outcomes such as objective response rate, duration of response, progression-free survival, and overall survival will also be recorded. The study involves close safety monitoring and follow-up throughout the treatment and observation periods.

Researchers are evaluating BGB-16673, an oral drug, in adults with various types of B-cell malignancies such as marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrm macroglobulinemia, diffuse large B-cell lymphoma, and Richters transformation. This study includes Phase 1 dose finding and safety expansion, followed by Phase 2 expansion cohorts to determine recommended doses and further assess safety and efficacy. The study is divided into several parts, starting with Phase 1 dose escalation to find safe dosage levels, including monotherapy dose escalation and safety expansion in selected doses. Phase 2 involves expansion cohorts where participants receive the recommended doses identified in Phase 1 for further safety and efficacy evaluation. Some cohorts include participants who have not received prior BTK inhibitors, and Japanese participants are also enrolled to assess safety. Treatments are orally administered. Participants will undergo regular assessments including monitoring for adverse events, disease response, and drug concentration levels in the blood at various time points. Researchers will measure outcomes such as overall response rate and progression-free survival over approximately three years. Safety and tolerability will be closely tracked, and quality of life questionnaires will be completed at scheduled intervals. Participation may last several years, including follow-up periods to monitor long-term effects.