A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies...
B-cell LymphomaNon-Hodgkin Lymphoma6 moreThis is an open-label, multicenter, Phase 1/2 study evaluating the safety and efficacy of CTX112™ in subjects with relapsed or refractory B-cell malignancies.
Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based...
LeukemiaLymphocytic2 moreBruton's tyrosine kinase inhibitors (BTKi), anti-CD20 antibodies, and the B cell lymphoma 2 inhibitor (BCL-2i) venetoclax are drug classes used to treat patients with chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). Anti-CD20 therapy may not be required for all patients. The investigators hypothesis is that it may be better to give anti-CD20 therapy (obinutuzumab) only to patients that still have detectable cancer in their blood (minimal residual disease [MRD]) after being treated with a combination of two oral medications, zanubrutinib (a BTKi ) and venetoclax (a BCL-2i), instead of giving a combination of three drugs to all patients from the start of treatment. This strategy, if effective, will prevent overtreatment with anti-CD20 antibodies; reduce side effects of treatment while potentially increasing MRD negativity rates; and will possibly make the anti-CD20 antibody therapy more effective given the low tumor burden present when utilized. This study will test this hypothesis by treating subjects with 3 cycles of a zanubrutinib monotherapy lead-in, in order to debulk and mitigate tumor lysis risk, followed by 13 cycles of zanubrutinib and venetoclax combination therapy. Subjects who are both peripheral blood and bone marrow MRD negative at the completion of the 13 cycles of combination therapy will stop treatment and enter an observation phase every 3 months. Subjects that are MRD positive will continue combination therapy with zanubrutinib and venetoclax for an additional 6 cycles but also receive 6 cycles of obinutuzumab in order to augment response and increase MRD negative rates for the overall treated cohort.
Anti-CD19 CAR-Engineered NK Cells in the Treatment of Relapsed/Refractory B-cell Malignancies
Acute Lymphocytic LeukemiaChronic Lymphocytic Leukemia1 moreThis study is a single arm, open and multi center exploratory clinical study to observe the safety and effectiveness of CAR NK-CD19 in participants with recurrent or refractory CD19 positive B-cell malignant tumors, and preliminarily evaluate the expansion of this product in vivo and the objective remission rate after administration.
Study of TBI-2001(Autologous CD19 Specific Chimeric Antigen Receptor (CAR) Gene-transduced T Lymphocytes)...
Relapsed or Refractory CD19+ B-cell LymphomaRelapsed or Refractory Chronic Lymphocytic Leukemia1 moreThis is a Phase 1/1b, open-label, dose-escalation study to evaluate the safety and the efficacy of anti-CD19 chimeric antigen receptor (CAR) (TBI-2001) for relapsed or refractory CD19+ B-cell lymphoma Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL).
Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL,...
Non-Hodgkin LymphomaChronic Lymphocytic Leukemia1 moreSubjects on this study have a type of lymph gland cancer called Non-Hodgkin Lymphoma, acute lymphocytic leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as "lymphoma" or "leukemia"). The lymphoma or leukemia has come back or has not gone away after treatment. The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Both antibodies and T cells have been used to treat patients with cancer. They have shown promise, but have not been strong enough to cure most patients. T cells can kill tumor cells but normally there are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person. The antibody used in this study is called anti-CD19. It first came from mice that have developed immunity to human lymphoma. This antibody sticks to lymphoma cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, anti-CD19 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. In the laboratory, the investigators found that T cells work better if they also add proteins that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells last longer in the body but not long enough for them to be able to kill the lymphoma cells. The investigators believe that if they add an extra stimulating protein, called CD137, the cells will have a better chance of killing the lymphoma cells. The investigators are going to see if this is true by putting the CD19 chimeric receptor with CD28 alone into half of the cells and the CD19 chimeric receptor with CD28 and CD137 into the other half of the cells. These CD19 chimeric receptor T cells with CD28 and with or without CD137 are investigational products not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to see how long the T cell with each sort of chimeric receptor lasts, to learn what the side effects are and to see whether this therapy might help people with lymphoma or leukemia.
CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or...
LymphomaNon-Hodgkin11 moreBackground: B-cell leukemias and lymphomas are cancers that are often difficult to treat. The primary objective of this study is to determine the ability to take a patient's own cells (T lymphocytes) and grow them in the laboratory with the CD19/CD22-CAR receptor gene through a process called 'lentiviral transduction (also considered gene therapy) and growing them to large numbers to use as a treatment for hematologic cancers in children and young adults.. Researchers want to see if giving modified CD19/CD22-CAR T cells to people with these cancers can attack cancer cells. In addition, the safety of giving these gene modified cells to humans will be tested at different cell doses. Additional objectives are to determine if this therapy can cause regression of B cell cancers and to measure if the gene modified cells survive in patients blood. Objective: To study the safety and effects of giving CD19/CD22-CAR T cells to children and young adults with B-cell cancer. Eligibility: People ages 3-39 with certain cancers that have not been cured by standard therapy. Their cancer tissue must express the CD19 protein. Design: A sample of participants blood or bone marrow will be sent to NIH and tested for leukemia. Participants will be screened with: Medical history Physical exam Urine and blood tests (including for HIV) Heart and eye tests Neurologic assessment and symptom checklist. Scans, bone marrow biopsy, and/or spinal tap Some participants will have lung tests. Participants will repeat these tests throughout the study and follow-up. Participants will have leukapheresis. Blood will be drawn from a plastic tube (IV) or needle in one arm then go through a machine that removes lymphocytes. The remaining blood will be returned to the participant s other arm. Participants will stay in the hospital about 2 weeks. There they will get: Two chemotherapy drugs by IV Their changed cells by IV Standard drugs for side effects Participants will have frequent follow-up visits for 1 year, then 5 visits for the next 4 years. Then they will answer questions and have blood tests every year for 15 years. ...
Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion...
Waldenstrom MacroglobulinemiaMultiple Myeloma7 morePart A of this study evaluates iopofosine I 131 (CLR 131) in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and central nervous system lymphoma (CNSL) who have been previously treated with standard therapy for their underlying malignancy. Part B (CLOVER-WaM) is a pivotal efficacy study evaluating IV administration of iopofosine I 131 in patients with WM that have received at least two prior lines of therapy.
Venetoclax With Ibrutinib or Acalabrutinib in Pts. With High-risk CLL
Chronic Lymphocytic LeukemiaThis is a single center, open-label, phase II study of venetoclax (ABT-199) added to ibrutinib or acalabrutinib in patients with high-risk CLL who have received at least 12 months of ibrutinib or acalabrutinib monotherapy. The study will estimate the therapeutic efficacy of venetoclax consolidation in patients who have detectable CLL after receiving ibrutinib or acalabrutinib for at least 12 months and who have high risk CLL.
Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing...
Acute Lymphoblastic LeukemiaAdult6 moreAdult patients with r/r acute lymphoblastic leukemia (ALL) (stratum I), r/r Non-Hodgkin's lymphoma (NHL) including chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) or mantle cell lymphoma (MCL) (stratum II) as well as paediatric patients with r/r ALL (stratum III) will be treated with autologous T-lymphocytes transduced by the third-generation RV-SFG.CD19.CD28.4-1BBzeta retroviral vector. The main purpose of this study is to evaluate safety and feasibility of escalating CD19.CAR T cell doses (0,1-20×20^7 transduced cells/m^2) after lymphodepletion with fludarabine and cyclophosphamide.
A Prospective Multicenter Phase 2 Study of FCR/BR Alternating With Ibrutinib in Treatment-naive...
Chronic Lymphocytic LeukemiaThis is a prospective multicenter phase 2 study designed with the purpose to evaluate the response rate and safety of treatment with FCR/BR alternating with ibrutinib in treatment-naive patients with chronic lymphocytic leukemia.