Active clinical trials for "Lymphoma"

Therapy for non-Hodgkin lymphoma (NHL) is in evolution as new molecular pathways and targeted therapies are identified. Although most NHLs respond to currently available therapies, the majority of patients relapse and many never have a complete response to therapy. In the investigators attempts to further understand the pathogenesis of NHLs, the investigators have identified and characterized expression of human endogenous retroviruses (HERVs) at the DNA, RNA and protein levels in association with the presence of NHLs (and other neoplastic diseases). The investigators preclinical evidence suggests a correlation with the level of HERV-K (a particular family of HERVs) expression and NHL disease activity, leading us to hypothesize that HERV-K expression may contribute to the development of the disease and/or to its recurrence. If this hypothesis is correct, then drugs that inhibit HERV-K expression may prevent recurrence of disease and/or may provide a novel therapeutic approach for NHLs. To test this hypothesis, the investigators eventually intend to study the use of anti-retroviral therapies in patients with NHL. The investigators in vitro studies have demonstrated that HERV-K expression decreases in response to the currently FDA-approved and available, anti-HIV drugs, Lamivudine and tenofovir disoproxil fumarate (tenofovir). These medications are tolerated well in HIV patients, but it is unknown how the combination of Lamivudine and Tenofovir will be tolerated by patients with NHL. To further test the investigators hypotheses, the investigators propose the following Specific Aims of the current study: (1) To evaluate the tolerability, toxicity and safety of administering Lamivudine and Tenofovir in combination to patients with relapsed or refractory NHL; (2) To evaluate the effects of the combination of lamivudine and tenofovir on HERV-K plasma viral RNA load; and (3) To monitor the response rate of the NHL to treatment with the combination of lamivudine and tenofovir. The investigators study will recruit adult patients with relapsed or refractory NHL whom the investigators have identified as having expression of HERV-K. Volunteer participants will be administered the combination of lamivudine and tenofovir and monitored for tolerability, toxicity, compliance, changes in viral RNA load and disease response.

RATIONALE: Collecting and studying tissue samples from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. PURPOSE: This research trial studies collecting tissue samples from patients with HIV-related malignancies.

Patients receive anti-CD19-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells over a period of 4 or 5 consecutive days in an escalating dose. After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 10 years.

This observational study will evaluate the safety and efficacy of MabThera/Rituxan (rituximab) in previously untreated patients with follicular lymphoma. Data will be collected for 3 years

Background: Allogeneic hematopoietic stem cell transplantation (or allotransplant; donor blood stem cells) have been used with varying degrees of success as an immune therapy for blood-system cancers (leukemias, myelodysplastic syndrome, lymphomas, multiple myeloma, etc.). Some people s cancer remains active (comes back or continues to spread) after an allotransplant, while other peoples cancer disappears and they are hopefully cured. National Institutes of Health (NIH) researchers are studying the reasons for these different treatment outcomes, and trying to develop better cancer treatments for people with active cancer after allotransplant. Researchers are collecting data from people who have had allotransplants for a cancer of the blood, whether or not the cancer is in remission, and from their donors. Those with active cancers may be eligible to participate in one of several NIH studies testing treatments for active cancer after allotransplant. Objectives: To develop a systematic, comprehensive evaluation of individuals with relapsed malignant blood cancers after allotransplant (and, if available, their donors) to identify potential treatment study options To compare the immune system after allotransplant between people whose cancers are growing with people whose cancers remain in remission. To compare the immune system after cancer relapse/progression treatment between people whose cancer responds to treatment with those whose cancers continue to grow. Eligibility: Individuals whose blood system cancer grows or comes back after receiving allotransplant treatment. Individuals whose blood system cancer is responding or in remission 100 days or more after receiving allotransplant treatment. Related stem-cell donors of eligible allotransplant recipients. Design: Participants will be evaluated with a full physical examination, detailed medical history (for recipients, including a history of allotransplant treatment process, side-effects, etc.), and blood tests. Recipients will also have imaging studies, possible tissue biopsies, quality of life questionnaires/assessments, and other tests to evaluate the current state of their cancer, whether active or in remission. In some cases, it may be possible to substitute results from recent tests and/or biopsies. Healthy related donors will have apheresis to provide white blood cells for study and/or for use in potential treatment options. If stem cells would be medically helpful to a recipient, their donors might be asked to take injections of filgrastim before the apheresis procedure to stimulate the production of stem cells for collection. As feasible, all recipients will be asked to return to the NIH for detailed follow-up visits in conjunction with 6, 12, and 24 months post-allotransplant evaluations, and may be monitored between visits. Recipients whose cancers are active and who are found to be eligible for treatment protocols at the NIH will continue to be monitored on this study while participating on treatment protocols. Return visits and follow-up tests for this study will be coordinated with those required by the treatment protocol. Participants may return in the future to be evaluated for new treatment study options (recipients) or additional cell donations for therapy (donors).

This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric Antigen Receptor (CAR) redirected allogeneic T-cells in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma.

This aim of this study to evaluate the safety and efficacy of combining a single course of Yttrium 90 Ibritumomab Tiuxetan, a radiolabeled monoclonal antibody ( Zevalin ), with high-dose BEAM chemotherapy and autologous peripheral stem cell transplantation in patients with relapsed, refractory, or transformed Non-Hodgkin's lymphoma.

RATIONALE: The CAT-8015 immunotoxin can bind tumor cells and kill them without harming normal cells. This may be effective treatment for Non-Hodgkin's lymphoma (NHL) that has not responded to chemotherapy, surgery or radiation therapy. PURPOSE: Phase 1 dose escalation study to determine the maximum tolerated dose of CAT-8015 immunotoxin in treating patients who have Non-Hodgkin's lymphoma and do not respond to treatment.

High-dose chemotherapy and autologous stem-cell transplantation have an established role in the treatment of aggressive Non-Hodgkin's lymphoma (NHL) when refractory to first line chemotherapy or after relapse. The PARMA study randomized 109 patients, with chemo-sensitive relapse and no marrow involvement to receive, following the initial salvage regimen, high-dose chemotherapy versus continuous standard dose chemotherapy. 5-year progression-free survival was 46% in the transplant group compared with 12% in the chemotherapy group. Results are significantly inferior in patients with multiply relapsed or chemo-refractory disease with only 0-20% of patients achieving long-term disease control with autologous transplantation. Thus a large proportion of patients with refractory and relapsing disease are not cured with currently available transplantation methods and newer approaches are required. Rituximab is the first monoclonal antibody approved for clinical use. It is an anti CD20 antibody with high response rate in the treatment of follicular lymphoma and increases response rate in aggressive lymphoma when combined with chemotherapy. It is well tolerated with minimal side effects. However tumors may escape rituximab sensitivity by loss of antigen, poor access of antibody to bulky or poorly vascularized tumors, or failure of host effectors to eliminate antibody binding tumor cells. Lymphoma cells are inherently and exquisitely sensitive to radiation. Radioimmunotherapy uses monoclonal antibodies conjugated with a radioactive isotope to target radiation directly to tumor cells. Ibritumomab is the parent murine anti CD20 antibody witch targets the same epitope as rituximab. Tiuxetan is a chelator covalently linked to the antibody which chelates the isotope 90Yttrium to form the active radioconjugate Zevalin. 90Yttrium is a pure high-energy beta emitter with a relatively short half time (64 hours) and a path length of 5 mm. These properties make it an ideal isotope for radioimmmunotherapy. The high energy and long beta path are advantageous in treating bulky, poorly vascularized tumors, and tumors with heterogeneous antigen expression as neighboring tumor cells can be hit by cross fire from tumors binding the radioconjugate. Pure beta emission limits radiation to the patient body and is safe for the surrounding allowing simple outpatient care, no need for patient isolation or shielding. Biodistribution is predictable, eliminating the need for dosimetry. Initial studies showed that Zevalin has a favorable toxicity profile and is more effective than rituximab in patients with follicular and transformed non-Hodgkin's lymphoma, and studies are currently performed in aggressive lymphoma. There are initial phase I-II studies combining radioimmunotherapy with high-dose chemotherapy and autologous stem-cell transplantation with promising results. We conducted a phase II study of fixed-dose Zevalin at 0.4 mCi/kg with BEAM high-dose chemotherapy in patients with chemo-refractory disease. So far, 23 patients were included. With a median follow-up of 17 months the estimated progression-free survival was 52% compared with 0-20% expected in patients with multiply relapsed and chemo-refractory disease. Based on these data and data from other groups we expect that the addition of Zevalin to standard high-dose chemotherapy will improve transplantation outcomes in patients with standard-risk chemosensitive disease, as well. This study will randomize patients to Zevalin-BEAM versus BEAM alone to determine the potential of Zevalin radioimmunotherapy to improve outcome of autologous stem-cell transplantation.

RATIONALE: Studying samples of semen from cancer survivors in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. PURPOSE: This phase I research study is looking at the presence of donor-derived DNA in semen samples form cancer survivors who underwent donor stem cell transplant.