This is a phase I/II study to evaluate the feasibility, safety and preliminary antitumor efficacy of rapcabtagene autoleucel (also known as YTB323). Rapcabtagene autoleucel will be investigated in combination with ibrutinib in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and as single agent in diffuse large B-cell lymphoma (3L+ DLBCL), adult acute lymphoblastic leukemia (ALL) and 1st Line High Risk Large B-Cell Lymphoma (1L HR LBCL).
The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will be tested either in Relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as: * Monotherapy, or * Combination therapy: * epcoritamab + venetoclax * epcoritamab + pirtobrutinib Treatment-naïve (TN) high risk (HR) (CLL): • epcoritamab + pirtobrutinib Combination therapy for Richter's Syndrome (RS): * epcoritamab + lenalidomide * epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine \[Oncovin®\] and prednisone). The study includes participants with R/R or TN HR CLL/small lymphocytic lymphoma (SLL) and participants with RS. The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Participants with RS are only included in the expansion phase. Epcoritamab will be injected subcutaneously (under the skin). Standard-of-care and combination treatments (venetoclax, pirtobrutinib, lenalidomide, and R-CHOP) will be given either orally (by mouth) or intravenously (in a vein). Study details include: * Study duration will be up to 5 years after the last participant's first treatment in the trial. * The treatment duration for each participant will be between 12 months (1 year) and 24 months (2 years), depending upon the treatment arm assigned. * The visit frequency will be either weekly, every other week, or monthly, depending upon the part of the study. All participants will receive active drug; no one will be given placebo.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. The purpose of this study is to assess how well ABBV-453 works adult participants with relapsed/refractory (R/R) untreated CLL/small lymphocytic lymphoma (SLL). Adverse events, pharmacokinetics, and change in disease activity will be assessed. ABBV-453 is an investigational drug for the treatment of CLL and SLL. There are 2 parts to this study. In part A participants will be placed 1 of 5 cohorts with a specific target dose for each cohort and receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the appropriate target dose is achieved. In part B participants will be placed in 2 cohorts and receive up to the maximum dose in part A, with cohort 2.1 including a debulking period (obinutuzumab) as in part A. Approximately 80 adult participants with previously R/R CLL/SLL will be enrolled in the study in approximately 40 sites across the world. Participants in part A will placed into 1 of 5 cohorts with a specific target dose for each cohort and will receive intravenous (IV) obinutuzumab as part of the debulking period, followed by escalating doses of oral ABBV-453 until the appropriate target dose is achieved. Participants in part B will be place in one of 2 cohorts. Participants in cohort 2.1 will receive IV obinutuzumab as part of the debulking period, followed by escalating doses of oral ABBV-453 until the maximum target dose from part A is achieved. Participants in cohort 2.2 will receive no treatment during the the debulking period, followed by escalating doses of oral ABBV-453 until the maximum target dose from part A is achieved. The estimated study duration is 5 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects.
This phase II trial studies how well venetoclax and ibrutinib work in treating patients with chronic or small lymphocytic leukemia. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax and ibrutinib may help control chronic or small lymphocytic leukemia.
This phase II trial studies how well acalabrutinib and venetoclax with or without early obinutuzumab work for the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma that is high risk, has come back (recurrent), or does not respond to treatment (refractory). Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax may stop the growth cancer cells by blocking BCL-2 protein needed for cell growth. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and venetoclax together with early obinutuzumab may improve clinical outcomes and control the disease.
This phase II trial studies how well zanubrutinib and rituximab work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma for which the patient has not received treatment in the past (previously untreated). Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. The study is being done to find out if zanubrutinib combined with rituximab can help control previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.
This phase II trial studies ibrutinib with or without rituximab in treating patients with chronic lymphocytic leukemia that has come back after treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether ibrutinib is more effective with or without rituximab in treating chronic lymphocytic leukemia.
This phase II trial studies how well ibrutinib, fludarabine phosphate, cyclophosphamide, and obinutuzumab work in treating patients with chronic lymphocytic leukemia. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving ibrutinib, fludarabine phosphate, cyclophosphamide, and obinutuzumab together may work better in treating chronic lymphocytic leukemia.
This phase II trial investigates the how well acalabrutinib and obinutuzumab work in treating patients with chronic lymphocytic leukemia (CLL). Acalabrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and obinutuzumab may help to control disease progression in CLL patients who have not received treatment for CLL.
To learn if the combination of LOXO-305 (pirtobrutinib) and venetoclax can help to control previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).