B Cell Lymphoma

The goal of this study is to compare how well sonrotoclax plus zanubrutinib works versus zanubrutinib plus placebo in treating adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL). This study will also look at the safety of sonrotoclax plus zanubrutinib versus zanubrutinib plus placebo.

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. About 90% of children and young adults who are treated for ALL can now be cured. But if the disease comes back, the survival rate drops to less than 50%. Better treatments are needed for ALL relapses. Objective: To test chimeric antigen receptor (CAR) therapy. CARs are genetically modified cells created from each patient s own blood cells. his trial will use a new type of CAR T-cell that is targeting both CD19 and CD22 at the same time. CD19 and CD22 are proteins found on the surface of most types of ALL. Eligibility: People aged 3 to 39 with ALL or related B-cell lymphoma that has not been cured by standard therapy. Design: Participants will be screened. This will include: Physical exam Blood and urine tests Tests of their lung and heart function Imaging scans Bone marrow biopsy. A large needle will be inserted into the body to draw some tissues from the interior of a bone. Lumbar puncture. A needle will be inserted into the lower back to draw fluid from the area around the spinal cord. Participants will undergo apheresis. Their blood will circulate through a machine that separates blood into different parts. The portion containing T cells will be collected; the remaining cells and fluids will be returned to the body. The T cells will be changed in a laboratory to make them better at fighting cancer cells. Participants will receive chemotherapy starting 4 or 5 days before the CAR treatment. Participants will be admitted to the hospital. Their own modified T cells will be returned to their body. Participants will visit the clinic 2 times a week for 28 days after treatment. Follow-up will continue for 15 years....

The purpose of this study is to find the best dose of the drug and measure the safety and efficacy of LY4152199 in participants with previously treated B-cell malignancies. Participants will have the option to continue taking LY4152199 until the study ends.

The goal of this study is to compare how well sonrotoclax plus zanubrutinib works versus zanubrutinib plus placebo in treating adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL). This study will also look at the safety of sonrotoclax plus zanubrutinib versus zanubrutinib plus placebo.

To learn if the combination of axicabtagene ciloleucel (axi-cel) and glofitamab as first-line therapy in high-risk LBCL participants or as second-line therapy in LBCL participants can help to control the disease.

The goal of this observational cohort study is to learn how toxin and occupational exposures, germline genetic variation, and immune dysregulation relate to B-cell non-Hodgkin lymphoma among active-duty service members and other Military Health System beneficiaries. The main questions are whether specific exposures and germline variants are associated with B-cell NHL subtype, immune dysfunction, and clinical outcomes. Participants will complete exposure and medical-history surveys, provide biospecimens for immune and genomic testing, and may be followed annually for up to 3 years.

The goal of this clinical research study is to learn about the safety of giving immune cells called natural killer (NK) cells with chemotherapy to patients with leukemia, lymphoma, or multiple myeloma. Immune system cells (such as NK cells) are made by the body to attack foreign or cancerous cells. Researchers think that NK cells you receive from a donor may react against cancer cells in your body, which may help to control the disease.

The use of venetoclax-based therapies for pediatric patients with relapsed or refractory malignancies is increasingly common outside of the clinical trial setting. For patients who cannot swallow tablets, it is common to crush the tablets and dissolve them in liquid to create a solution. However, no PK data exists in adults or children using crushed tablets dissolved in liquid in this manner, and as a result, the venetoclax exposure with this solution is unknown. Primary Objectives • To determine the pharmacokinetics of venetoclax when commercially available tablets are crushed and dissolved into a solution Secondary Objectives * To evaluate the safety of crushed venetoclax tablets administered as an oral solution * To determine the pharmacokinetics of venetoclax solution in patients receiving concomitant strong and moderate CYP3A inhibitors * To determine potential pharmacokinetic differences based on route of venetoclax solution administration (ie. PO vs NG tube vs G-tube) * To determine the concentration of venetoclax in cerebral spinal fluid when administered as an oral solution

The purpose of this study is to measure the safety, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics with BGB-16673 in combination with other agents in participants with relapsed or refractory (R/R) B-cell malignancies. This study is structured as a master protocol with separate substudies. This study currently includes four substudies, and more substudies may be added as other combination agents are identified.

This is a first-in-human, multicenter, open-label, single-arm Phase I study of FXS0683 in participants with relapsed or refractory hematologic malignancies to evaluate safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity, and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

To learn if giving mosunetuzumab in combination with polatuzumab vedotin, tafasitamab, and lenalidomide can help to control relapsed/refractory FL and DLBCL.

Bendamustine and the combination of fludarabine/cyclophosphamide are fully authorized chemotherapy agents in Switzerland for lymphoma treatment and currently used in routine clinical practice as lymphodepletion strategy before CAR-T immunotherapy, as supported by retrospective studies and clinical experience across multiple centers. None of the drugs described in this protocol are being used at unapproved doses, or in an investigational formulation. Both lymphodepletion regimens have a known safety profile and the risks and burdens imposed on participants do not exceed those encountered in routine CAR-T therapy management, as all procedures (including monitoring, supportive care, and follow-up assessments) align with standard clinical practice. Based on these assumptions, this protocol is designed to investigate the use of bendamustine as an alternative lymphodepletion therapy (which is a part of CAR-T immunotherapy protocol).

1. Study Title: A Study on the Efficacy and safety of Autocrine p40-Expressing CD19-Targeted Chimeric Antigen Receptor T Cells (CD19-CAR.p40-T) in Patients With Relapsed/Refractory CD19-Positive Hematologic Malignancies 2. Study Objectives: 2.1.1 Primary Objective To evaluate the safety of autocrine p40-expressing CD19-targeted chimeric antigen receptor T cells (CD19-CAR.p40-T) in the treatment of patients with relapsed/refractory CD19-positive hematologic malignancies. 2.1.2 Secondary Objective To evaluate the efficacy of autocrine p40-expressing CD19-targeted chimeric antigen receptor T cells (CD19-CAR.p40-T) in the treatment of patients with relapsed/refractory CD19-positive hematologic malignancies. 2.1.3 Exploratory Objective To evaluate the in vivo expansion and persistence of CD19-CAR.p40-T cells. 3. Participant Intervention: Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and -3 relative to the planned CD19-CAR.p40-T cell infusion. The CD19-CAR.p40-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.

This is a single-arm, open-label clinical study evaluating the efficacy and safety of U01 (ssCART-19) in patients with relapsed or refractory B-cell lymphoma.

Patients will receive one of two conditioning regimens (BEAM or CBV) before receiving an autologous stem cell transplant (ASCT). If patients achieve either complete, partial, or stable response following ASCT, they will receive an IV dose of Polatuzumab Vedotin once every 21 days until they receive 8 doses. After Polatuzumab Vedotin therapy is completed, patients will be followed every 4 months for about 2 years.

The study will evaluate NX-5948 (bexobrutideg) in combination with venetoclax with or without an anti-CD20 antibody (rituximab or obinutuzumab) in second-line or higher (2L+) relapsed/refractory (R/R) or first-line (1L) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

This first-in-human (FIH) trial is designed to assess the safety, feasibility and preliminary efficacy of a single intravenous (IV) dose of SynKIR-310 administered to participants with relapsed/refractory B-NHL.

The study will evaluate the efficacy and safety of NX-5948 (bexobrutideg) versus pirtobrutinib in participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who are relapsed or refractory to prior covalent Bruton tyrosine kinase inhibitor (cBTKi) treatment.

This is a phase I dose-finding trial of an autologous CD22 targeting chimeric antigen receptor (CAR)-T cell product, called CLIC-2201, for participants with relapsed/refractory B cell malignancies. In the proposed trial, eligible enrolled participants will undergo leukapheresis for autologous T cell collection to enable CLIC-2201 manufacturing, followed by lymphodepletion with cyclophosphamide and fludarabine, then intravenous infusion of the autologous CLIC-2201 product. The trial will use the 3+3 design to escalate or de-escalate the dose level of CLIC-2201 administered. Participants will be monitored for safety and tolerability up to day 365 following CLIC-2201 infusion. The primary objective is to evaluate the safety and tolerability of CLIC-2201 and estimate the maximum tolerated dose (MTD) of CLIC-2201 in B-cell malignancies. The secondary objectives are to evaluate the (i) feasibility; (ii) anti-tumour activity of CLIC-2201; (iii) and characterize the pharmacokinetic (PK) profile of CLIC-2201. Exploratory objectives will include: i) characterizing the cellular and humoral immune responses against CLIC-2201 up to 1 year following infusion of CLIC-2201; (ii) characterizing the phenotype and gene expression profile of CLIC-2201 cells; (iii) evaluating immune and tumour cells at baseline and relapse for biomarkers of response or toxicity; (iv) evaluating serum cytokines, circulating tumour DNA (ctDNA) and B cell aplasia as biomarkers of clinical outcomes; and (v) assessing the quality of life.

The purpose of this study is to evaluate the safety and tolerability of BAFF-R CAR-T Cells in Adult Subjects with CD19-Negative relapsed or refractory B-Cell Lymphoma.

This is a Phase II single-center open label trial of the combination of ATRA and pembrolizumab treatment in patients with histologically proven, relapsed or refractory Hodgkin Lymphoma or B-Non-Hodgkin-lymphoma.

The purpose of the study is to establish the safety and efficacy of zanubrutinib in combination with rituximab for people with untreated B-cell lymphomas (marginal zone lymphoma and follicular lymphomas).

This is an open label, single-site, dose-escalation study in up to 18 participants with treatment of relapsed/refractory B-cell lymphoma. This study aims to evaluate the safety and efficacy of the treatment with an Anti- CD19 gene injection

BrUOG-401 is a prospective, single-arm, phase 2 trial of first-line therapy in adult patients with previously untreated FL or MZL. All patients will be assigned the same initial treatment plan, modified by interim response assessment (IRA) after Cycle 4. All patients will start treatment with four 21-day cycles (C1-4) of mosunetuzumab alone (using step-up dosing during C1), followed by IRA. Patients who achieve CR at IRA will continue with additional 4 cycles (C5-8) of mosunetuzumab. Patients who achieve PR at IRA will receive mosunetuzumab with lenalidomide augmentation during C5-8. Primary response assessment (PRA) will occur after C8. Patients who remain in PR at PRA will continue for additional 4 cycles (extended augmentation).

This study is to provide locally produced, bispecific CD19 CD20 CAR T cells to patients with B-cell lymphoma/leukemia who have no access to commercial CAR T cells or who have relapsed thereafter. The primary objective is to assess the safety of bispecific anti-CD19, anti- CD20 CAR T cell-therapies after lymphodepleting chemotherapy in patients with B cell malignancies with exhausted standard treatment options.