View clinical trials related to Lymphoma, Non-Hodgkin.
Filter by:To determine whether zidovudine (AZT) in conjunction with bone marrow transplantation prevents the reinfection of donor hematopoietic/lymphoid cells in patients with positive HTLV III antibody and large cell/diffuse histiocytic lymphoma. Patients who are candidates will be evaluated for HTLV III activity and drug levels.
The purpose of this study is to see if it is safe and effective to use gene therapy to treat non-Hodgkin's lymphoma (NHL) in HIV-positive patients. Stem cell transplantation is a procedure used to treat NHL. Stem cells are very immature cells that develop to create all of the different types of blood cells. In this study, some of your stem cells will be treated with gene therapy, meaning the cells are treated with a virus that does not cause disease. Some cells will receive a virus that contains ribozymes, enzymes that may help fight HIV. Other cells will be treated with a virus that does not contain ribozymes to see how the virus works alone. Some cells will not be treated at all. Doctors would like to see whether giving patients stem cells with ribozymes can treat NHL and stop HIV from growing at the same time.
To determine the efficacy and toxicity of the combination of mitoxantrone hydrochloride ( Novantrone ) and etoposide in the treatment of patients with HIV associated lymphomas.
Allogeneic peripheral blood stem cell transplantation (PBSCT) is primarily limited by graft-versus-host disease (GVHD). In murine models, we have demonstrated that donor CD4+ T cells of Th1 cytokine phenotype (defined by their secretion of IL-2 and IFN-gamma) mediate GVHD. In contrast, donor CD4+ T cells of Th2 phenotype (defined by their secretion of IL-4, IL-5, and IL-10) do not generate GVHD, and abrogate Th-1-mediated GVHD. Importantly, we have demonstrated that enrichment of murine allografts with Th2 cells reduces GVHD without impairing the ability of donor T cells to prevent graft rejection. These studies indicate that the administration of Th2 cells after allogeneic transplantation represents a strategy for achieving alloengraftment with reduced GVHD. In addition to GVHD, allogeneic PBSCT has been limited by the toxicity associated with conventional myeloablative preparative regimens. Such regimens, which typically utilize total body irradiation (TBI) and high-dose chemotherapy, were once considered essential for the prevention of graft rejection. However, recent clinical studies have shown that non-myeloablative doses of fludarabine-based chemotherapy can result in alloengraftment. In murine models, we have demonstrated that severe host T cell depletion induced by combination fludarabine and cytoxan can prevent even fully-MHC mismatched marrow graft rejection. Although non-myeloablative regimens may reduce regimen-related toxicity, such transplants have been associated with a 30 to 40% incidence of severe acute GVHD that is similar to rates observed with myeloablative regimens. Because non-myeloablative regimens appear to be associated with reduced regimen-related toxicity, we have elected to conduct this phase I study of Th2 cells in the setting of an immunoablative (non-myeloablative) preparative regimen. Patients with leukemia in clinical remission, and patients with refractory lymphoid malignancy will be candidates for this HLA-matched allogeneic PBSCT protocol. Patients will receive novel induction regimen (fludarabine and EPOCH) and transplant preparative regimen (fludarabine and cytoxan) designed to maximally deplete host immune T cells capable of mediating graft rejection. After induction and preparative regimen chemotherapy, patients will receive an unmanipulated, G-CSF mobilized PBSC graft. In the initial six patients receiving this transplant procedure at the NCI, graft rejection has been successfully prevented (100% donor chimerism by day 30 post-transplant). Importantly, GVHD has been observed in all six patients, with three of the six patients developing severe GVHD (grade III). Given that this regimen successfully achieves donor engraftment, and is associated with significant GVHD, this transplant regimen represents an excellent clinical setting for the evaluation of Th2 cells. Using this non-myeloablative allogeneic PBSCT approach, we will perform a Phase I study to evaluate the safety and feasibility of administering donor Th2 cells on day 1 post-transplant. Prior to transplantation, donor CD4+ T cells will be stimulated in vitro using culture conditions that support the generation of donor CD4 cells of the Th2 cytokine profile. If this Phase I study demonstrates that Th2 cell administration is safe and feasible, a Phase III study will be performed to evaluate whether Th2 cell administration reduces the incidence and severity of GVHD. Successful implementation of this Th2 strategy will greatly reduce the morbidity and mortality associated with allogeneic PBSCT, and may also represent an approach to stem cell transplantation in patients lacking an HLA-matched donor.
This study will examine the use of a radioactive monoclonal antibody called yttrium 90-labeled humanized anti-Tac (90 Y-HAT) for treating certain cancers. Monoclonal antibodies are genetically engineered proteins made in large quantities and directed against a specific target in the body. The anti-Tac antibody in this study is targeted to tumor cells and is tagged (labeled) with a radioactive substance called Yttrium-90 (Y-90). The study will determine the maximum tolerated dose of 90Y-HAT and examine its safety and effectiveness. Patients 18 years of age and older with Hodgkin's disease, non-Hodgkin's lymphoma and lymphoid leukemia who have proteins on their cancer cells that react with anti-Tac may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), chest x-ray, computed tomography (CT) scan or ultrasound of the abdomen, positron emission tomography (PET) scan of the neck and body, and skin test for immune reactivity to antigens (similar to skin tuberculin test). Before beginning treatment, participants may undergo additional procedures, including the following: - Patients with suspicious skin lesions have a skin biopsy. An area of skin is numbed and a circular piece of skin about 1/4-inch diameter is removed with a cookie cutter-like instrument. - Patients with hearing loss have a hearing test. - Patients with neurological symptoms have a lumbar puncture (spinal tap). A local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle. - Patients who have not had a bone marrow biopsy within 6 months of screening also undergo this procedure. The skin and bone at the back of the hip are numbed with a local anesthetic and a small piece of bone is withdrawn through a needle. Patients receive 90 Y-HAT in escalating doses to determine the highest dose that can be safely given. The first group of three patients receives a low dose and, if there are no significant side effects at that dose, the next three patients receive a higher dose. This continues with subsequent groups until the maximum study dose is reached. 90 Y-HAT is given through a vein (intravenous (IV)) over a 2-hour period. In addition, a drug called Pentetate Calcium Trisodium Inj (Ca-DTPA) is given via IV over 5 hours for 3 days to help reduce the side effects of the 90Y-HAT. In some patients, the 90 Y-HAT may also be attached to a radioactive metal called Indium-111 to monitor what happens to the injected material. During infusion of the drug, patients undergo PET scanning to trace the path of the injected material in the body. For this procedure, the patient lies in the scanner, remaining in one position during the entire infusion. Blood and urine specimens are collected periodically over a 6-week period following the infusion to determine the level of the radioactive antibody. Bone marrow, lymph node, or skin biopsies may be done to determine how much of the antibody entered these sites. Patients whose disease remains stable or improves with therapy may receive up to six more infusions of 90 Y-HAT, with at least a 6-week interval between treatments.
Non-Hodgkin's lymphoma (NHL) is the third most rapidly increasing cancer in the United States. HIV-related NHL is responsible for some of the increase since the early 1980s. However, it cannot explain the steady increase in the incidence rates in earlier years, nor the entire increase shown recently. A possible role of environmental exposures is receiving attention. One possibility is that exposure to organochlorines (OCs) may be related to the occurrence of NHL. NCI is currently designing a large population-based case-control study to investigate this hypothesis further by analyzing OC levels in blood collected at the time of interview from cases of NHL and their matched controls. At the time of these interviews, cases in the main case-control study would most likely have already received chemotherapy. If chemotherapy changes the blood levels of OCs, this may lead to misclassification of exposure among cases and eventually to biased risk estimates. The purpose of this pilot study is to estimate the bias due to measuring the serum levels of OCs in cases during or after chemotherapy. Twenty newly diagnosed patients will be recruited for the study. From each patient, four consecutive blood samples, one prior to, two during, and one after chemotherapy, will be collected. Forty pairs of pre-existing cryopreserved serum samples (pre- and post-treatment) taken from the NHL patients who participated in an earlier NCI clinical study will also be included in this study. Samples will be assayed for OC levels. The results will be used to plan and to interpret another large case-control study (the main study).
This is a randomized study of combination chemotherapy (EPOCH II) versus EPOCH II and immunotherapy with peripheral blood stem cells (PBSC) and IL-2 in patients with relapsed Hodgkin's and non-Hodgkin's lymphomas, and untreated patients with low-grade non-Hodgkin's lymphomas. The chemotherapy entails the administration of multiple cycles of infusional doxorubicin, etoposide and vincristine chemotherapy (total of 3), alternating with cycles of high-dose cyclophosphamide (3 cycles). Patients will be randomized, on a 2:1 basis, to either receive only chemotherapy or to undergo a PBSC harvest with PBSC reinfusion and IL-2 following the last cycle of chemotherapy. In all patients, immunological monitoring for NK/LAK activity, T cell number and function will be performed. The therapy is specifically targeted for patients who would be candidates for high-dose chemotherapy with stem cell support.
5-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation. EPOCH: Etoposide, VP-16, NSC-141540; Prednisone, PRED, NSC-10023; Vincristine, VCR, NSC-67574; Cyclophosphamide, CTX, NSC-26271; Doxorubicin, DOX, NSC-123127; with Granulocyte Colony-Stimulating Factor (Amgen), G-CSF, NSC-614629....
Non-Hodgkin's lymphoma has been studied in the Pediatric Branch for at least 20 years, during which time a number of different treatment protocols have been used. Approximately 110 patients have apparently been cured of their lymphoma. The present protocol has no therapeutic component, but is designed to document the late effects that may have been encountered by our patients, either as a consequence of the disease or its treatment. In essence, patients who consent to participate will be asked a series of questions pertaining to the quality of their life and possible medical problems that they may be encountering. In addition, they will receive a complete physical examination and undergo non-invasive investigations designed to identify the presence of unsuspected late effects. Investigators in the Eye Clinic, Dental Clinic, Audiology, Cardiology and Endocrinology departments will participate in the protocol. As a part of the study, blood samples will be obtained to investigate the possibility that predisposing genetic factors may be identifiable in the patients normal cells (e.g., p53 mutations, evidence of DNA instability). If such abnormalities are detected, blood samples from family members will also be examined to determine whether the defect was inherited.
Major improvements in the treatment of childhood non-lymphoblastic lymphomas have taken place in the last ten years. Though the survival rate in low risk patients (i.e., those with stage I & II disease and serum LDH of less than 350 IU/dL) was as high as 90% with the previous Pediatric Branch protocol, only 32% of patients in the high risk group achieved long term remission. The present protocol is designed to improve survival in the high risk group by using alternating non-cross resistant drug regimens. We plan to determine whether using granulocyte-macrophage colony stimulating factor (GM-CSF) in this group would increase dose-intensity and ameliorate myelotoxicity. We also plan to study the effect on survival of decreasing the duration of treatment to three months from the present year-long therapy in low-risk patients.