Valchlor

This research study is being conducted to evaluate an experimental drug called huCART19-IL18-CD428z cells in patients living with HIV who have been diagnosed with Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Acute Lymphoblastic Leukemia (ALL), and Richter's Transformation (RT).

This phase II trial tests how well tacabrutideg and sonrotoclax, with response-guided addition of obinutuzumab, works in treating patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Tacabrutideg is a drug that degrades a protein called Bruton's tyrosine kinase (BTK). By degrading BTK, tacabrutideg inhibits the activation of signaling pathways that help cancer cells survive, inhibiting the growth of cancer cells that express the BTK protein. Sonrotoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving tacabrutideg together with sonrotoclax may kill more cancer cells than giving either drug alone, and giving obinutuzumab after initial treatment with tacabrutideg and sonrotoclax may improve disease response in patients whose CLL or SLL didn't respond completely to initial treatment.

This is a phase 2, single-arm, open-label clinical trial determining efficacy of Epcoritamab in subjects with Chronic Lymphocytic Leukemia (CLL) on Burton Tyrosine Kinase Inhibitor (BTKi).

Background: Chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) are diseases in which the body makes too many white blood cells that do not work properly. Because white cells play a role in immune function, people with CLL/SLL may be at greater risk of infections. CLL/SLL can be controlled with drugs, but many people develop resistance, and the treatments stop working. Objective: To test a new drug (nemtabrutinib) in people with CLL/SLL. Eligibility: People aged 18 years or older with CLL/SLL that persists despite treatment. Design: Participants will be screened. They will have imaging scans, blood and urine tests, and a test of their heart function. They will have a bone marrow biopsy: a sample of tissue and fluids will be drawn from inside their hip bone. They may also have a sample cut from a swollen lymph node, if one is safe to access. Nemtabrutinib is a tablet taken by mouth. Participants will take the drug once a day at home in 4-week cycles. They will have clinic visits at least every 4 weeks for the first 6 months and then every 3 months after that. Biopsies, imaging exams, and other tests may be repeated at these visits. Participants may also undergo lymphapheresis: Blood will be drawn from a tube inserted into a vein. The blood will pass through a machine that separates out cancer and immune cells. The remaining blood will be returned to the body through a different tube. Participants may stay in the study as long as the drug is helping them.

This is a single-arm, open-label Phase 2 study designed to evaluate the treatment outcomes of nemtabrutinib-venetoclax-obinutuzumab as a frontline management for chronic lymphocytic leukemia (CLL).

Therapy with chimeric antigen receptor T (CAR-T) cells has demonstrated activity against refractory hematologic malignancies, however not all tumors respond or remain in response to CD19 targeted CAR-T cells. We posit that CAR-T cells expressing BAFF (BAFF CAR-T cells) can become another strategy to treat refractory hematologic malignancies, even after relapse following cluster of differentiation antigen 19 (CD19) targeting CAR-T treatment. This phase 1 study will evaluate safe dose and provide initial signal of the activity of BAFF CAR-T cells against refractory hematologic malignancies using a single lymphodepletion regimen and using a BAFF CAR-T cell manufacturing process.

The goal of this clinical research study is to learn if the combination of zanubrutinib, sonrotoclax, and obinutuzumab can help to control previously untreated CLL/SLL.

This phase II trial tests the safety, side effects and how well giving tafasitamab with acalabrutinib and venetoclax works for the treatment of chronic lymphocytic leukemia (CLL)/small cell lymphoma (SLL). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Tafasitamab is a monoclonal antibody that binds to CD19 antigen which is found on the surface of most B cells (a type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantle cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving tafasitamab with acalabrutinib and venetoclax may be safe and effective for treating patients with CLL/SLL.

This Phase II hybrid decentralized multicenter study examines the outcomes of stopping Bruton tyrosine kinase inhibitor (BTKi) therapy in patients with chronic lymphocytic leukemia (CLL) who have remained in remission for at least two years. The primary objective is to determine how long patients remain free from disease progression or death after discontinuing treatment, measured as event free survival. The study also evaluates whether stopping BTKi therapy leads to improvements in quality of life and reductions in treatment related side effects. Researchers will follow patients over time to assess if the cancer returns, whether resistance to therapy develops, and how patients feel during the treatment free period. In addition, the trial will investigate how discontinuing BTKi therapy affects immune function, including whether immune recovery occurs and infection risk decreases. Preliminary data indicate that patients may experience a treatment free interval exceeding two years after stopping therapy, with associated improvements in quality of life. By prospectively evaluating a time limited treatment strategy, this trial aims to determine whether durable disease control can be maintained off therapy while also assessing the resolution of BTKi related adverse events and changes in patient reported outcomes. Overall, the study seeks to determine whether patients can safely discontinue BTKi therapy and potentially restart treatment later if needed, thereby maintaining disease control while reducing the burden of continuous therapy.

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).

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 3, randomized, open-label, multicenter study comparing rocbrutinib (LP-168) versus pirtobrutinib in adult participants with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received a covalent Bruton's tyrosine kinase inhibitor (cBTKi). Approximately 306 participants will be randomized 1:1 to receive rocbrutinib 200 mg orally once daily or pirtobrutinib 200 mg orally once daily, administered continuously in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. Randomization will be stratified by presence of del(17p)/TP53 mutation (yes/no), reason for discontinuation of prior cBTKi therapy (toxicity vs disease progression), prior exposure to a BCL2 inhibitor (yes/no), and region (United States/China/rest of world). The primary endpoint is progression-free survival (PFS) assessed by an independent review committee (IRC) using iwCLL 2018 criteria for CLL and Lugano 2014 criteria for SLL. Key secondary objectives include overall survival, overall response rate, time-to-event outcomes, and safety/tolerability; exploratory objectives include health-related quality of life and biomarker assessments.