Active clinical trials for "Lymphoma, Large B-Cell, Diffuse"

Obatoclax may stop the growth of non-Hodgkin lymphoma by blocking blood flow to the cancer. Bortezomib and obatoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving obatoclax together with bortezomib may kill more cancer cells. This phase I/II trial is studying the side effects and best dose of obatoclax when given together with bortezomib and to see how well they work in treating patients with aggressive relapsed or recurrent non-Hodgkin lymphoma.

This is a Phase II, single institution, single-arm, open-label study of oral dasatinib monotherapy administered to subjects with relapsed or refractory aggressive DLBCL. This study will be conducted in two phases: a Treatment Phase and a Follow-up Phase. Research Hypothesis: Dasatinib, when administered orally at a continuous dose of 100 mg once daily, will be safe and effective in treating subjects that have failed prior therapies to diffuse large B cell lymphoma (DLBCL) or have relapsed disease.

This phase I trial is studying the side effects and best dose of giving tanespimycin together with bortezomib in treating patients with advanced solid tumors or lymphomas. (Accrual for lymphoma patients closed as of 11/27/09) Drugs used in chemotherapy, such as tanespimycin, work in different ways to stop cancer cells from dividing so they stop growing or die. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It may also increase the effectiveness of tanespimycin by making cancer cells more sensitive to the drug. Combining tanespimycin with bortezomib may kill more cancer cells.

Background: Improved treatments for a variety of treatment-resistant, TNFRSF8 (CD30)-expressing malignancies including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing lymphomas are needed. T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens. Autologous T cells genetically modified to express CARs targeting the B-cell antigen B-lymphocyte antigen CD19 (CD19) have caused complete remissions in a small number of patients with lymphoma. These results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in humans. CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which allows selection of CD30-expressing malignancies for treatment. CD30 is not known to be expressed by normal cells except for a small number of activated lymphocytes. We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice. This particular CAR has not been tested before in humans. Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of a small number of normal activated lymphocytes is possible, and unknown toxicities are also possible. Objectives: Primary -Determine the safety and feasibility of administering T-cells expressing a novel fully human anti-CD30 CAR to patients with advanced CD30-expressing lymphomas. Eligibility: Patients must have anaplastic large cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy associated T-cell lymphoma, or extranodal natural killer (NK)/T-cell lymphoma, nasal type Patients must have malignancy that is both measurable on a computed tomography (CT) scan with a largest diameter of at least 1.5 cm and possessing increased metabolic activity detectable by positron emission tomography (PET) scan. Alternatively, patients with lymphoma detected by flow cytometry of bone marrow are eligible. Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection fraction. An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 is required. No active infections are allowed including evidence of active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. At the time of protocol enrollment patients must be seronegative for cytomegalovirus (CMV) by antibody testing or must have a negative blood CMV polymerase chain reaction (PCR). Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated. At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and initiation of required leukapheresis. Clear CD30 expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment. Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-CD20 monoclonal antibody. Patients who have never had an allogeneic hematopoietic stem cell transplant as well as patients who have had a 9/10 or 10/10 human leukocyte antigen (HLA)-matched sibling or a 9/10 or 10/10 HLA- matched unrelated donor hematopoietic stem cell transplant are potentially eligible. Women who are pregnant or plan to become pregnant will be excluded.

Single center, phase I/II trial of pembrolizumab after CTL019 for CD19+ lymphomas. Patients will have CD19+ diffuse large B-cell, follicular, or mantle cell lymphomas relapsed/refractory after CTL019. 12 total patients will be enrolled. Safety of pembrolizumab (primary endpoint) will be determined using a Bayesian monitoring rule for treatment-related adverse events causing drug discontinuation. Secondary efficacy endpoints include overall response rate and progression-free survival.

There are 2 parts to this study: Part 1 (dose de-escalation) and Part 2 (dose expansion). The goal of Part 1 of this clinical research study is to find the highest tolerable dose of lenalidomide in combination with obinutuzumab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) that can be given to patients with diffuse large B cell lymphoma. The goal of Part 2 of this clinical research study is learn if the dose of lenalidomide found in Part 1 can help to control the disease. The safety of this drug combination will be studied in both parts.

The purpose of this study is to evaluate the safety, tolerability, and efficacy of MEDI4736 (durvalumab) alone and in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory dIffuse large B-cell lymphoma.

Objectives of this clinical trial are to evaluate the safety, tolerability, pharmacokinetics and potential efficacy of the investigational drug, cobomarsen (MRG-106), in patients diagnosed with certain lymphomas and leukemias, including cutaneous T-cell lymphoma (CTCL) [mycosis fungoides (MF) subtype], chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) [activated B-cell (ABC) subtype], and adult T-cell leukemia/lymphoma (ATLL). Cobomarsen is an inhibitor of a molecule called miR-155 that is found at high levels in these types of cancers and may be important in promoting the growth and survival of the cancer cells. Participants in the clinical trial will receive weekly doses of cobomarsen administered by injection under the skin or into a vein, or by injection directly into cancerous lesions in the skin (for CTCL only). Blood samples will be collected to measure how cobomarsen is processed by the body, and other measurements will be performed to study how normal and cancerous cells of the immune system respond when exposed to cobomarsen.

Part 1 (Phase Ib) Primary objective: To establish the maximum tolerated dose (MTD) of BI 836826 in combination with GemOx. Secondary objectives: To evaluate pharmacokinetics of BI 836826 when given in combination with GemOx and to investigate preliminary efficacy in terms of the overall response rate based on investigator's assessment. Part 2 (Phase II randomized) Primary objective: To investigate the efficacy by means of the overall response rate (PR+ CR) based on central review assessment in patients with relapsed DLBCL treated with BI 836826-GemOx compared to R-GemOx. Secondary objective: To investigate the efficacy by means of the complete remission rate based on central review assessment in patients with relapsed DLBCL treated with BI 836826-GemOx compared to Rituximab + gemcitabine + oxaliplatin (RGemOx).

This phase II trial studies how well tacrolimus, bortezomib, and anti-thymocyte globulin (thymoglobulin) work in preventing low toxicity graft versus host disease (GVHD) in patients with blood cancer who are undergoing donor stem cell transplant. Tacrolimus and anti-thymocyte globulin may reduce the risk of the recipient's body rejecting the transplant by suppressing the recipient's immune system. Giving bortezomib after the transplant may help prevent GVHD by stopping the donor's cells from attacking the recipient. Giving tacrolimus, bortezomib, and anti-thymocyte globulin may be a better way to prevent low toxicity GVHD in patients with blood cancer undergoing donor stem cell transplant.