Active clinical trials for "Lymphoma, AIDS-Related"

RATIONALE: Donor peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Treatment with donor white blood cells may prevent this from happening. PURPOSE: Phase II trial to study the effectiveness of donor peripheral stem cell transplantation followed by infusions of donor white blood cells in treating patients who have AIDS-related lymphoma.

The purpose of this study is to find out why cancers develop in HIV-positive patients. Cancer is a leading cause of death in AIDS patients. Common cancers in HIV-infected patients include Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), a cancer of the immune system. Risk factors include certain chemicals, viruses, and perhaps even anti-HIV drugs. Doctors would like to find out which risk factors are most important and how they relate to cancer in AIDS patients.

The incidence of lymphomas is increased among HIV infected patients. In 70 % of cases, those are Non Hodgkin's lymphomas (NHL) and Hodgkin lymphomas (HL) in 30% of cases. In France, their incidence is estimated to 100 cases per year (data from the "Base de données Hospitalière Française sur l'Infection à VIH" (FHDH)). The main mechanisms involved in lymphomagenesis are immune dysfunction, involvement of oncogenic viruses (Epstein-Barr (EBV) and HHV8) and molecular oncogenic events. A better understanding of these different pathways, give the possibility to design specific treatments. The treatment of these lymphomas is not standardized. A prospective study of patients with HIV associated lymphoid malignancies is an innovating tool to answer epidemiological, physiopathological and therapeutic questions. We propose a prospective multicentric study of these patients. The main objectives of this prospective study are to: evaluate the incidence, characterise clinically and histologically NHL and HL cases associated to HIV perform an observational study of the treatment and outcome of these patients out of the context of clinical trials, study the differentiation and activation of B-cell populations, better understand the role of specific T cell responses in the control of EBV infection, allow other biological studies from the ANRS group " Lymphome et VIH ". The recruitment of 40 cases per year is expected. The length of inclusions is 7 years. The follow-up will be of 2 years. Clinical, pathological and biological data at diagnosis and during follow-up will be collected. This will allow characterizing the lymphoma, the HIV infection, the antitumoral treatments and the outcome of lymphoma. Biological samples will be centralized to collect cell, DNA, RNA, plasma, serum and tumour collections (Y.Taoufik, S Prevot* ). To better understand the EBV infection and lymphomagenesis in HIV infection, we propose to follow the viral load and the molecular characteristics of EBV in PBMC, plasma and tumour (P.Morand* , V.Boyer* ), to investigate the EBV-T cell responses (G.Carcelain) and the presence and reactivation of EBV in peripheral B cells (C.Amiel* , JC Nicolas) and in tumoral samples (M.Raphael* , I.Joab* ). The other mechanisms of lymphomagenesis in HIV infection will be studied by the analysis of the sub-populations of B-cells in terms of activation and differentiation (Y.Taoufik) and by the characterization of MSI tumours (A.Duval).

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 study will evaluate the usefulness of two tests in quickly distinguishing whether a patient with HIV infection and focal brain lesions (an injury in a specific area of the brain) has a rare type of cancer called primary central nervous system lymphoma (PCNSL), or a parasitic infection called toxoplasmic encephalitis. Toxoplasmic encephalitis is caused by a parasite and can be treated with antibiotics. PCNSL (lymphoma of the brain or spinal cord) must be definitively diagnosed with a brain biopsy (removal of a small piece of brain tissue), and the treatment is radiation therapy and chemotherapy. The tests under study for diagnosing PCNSL or toxoplasmic encephalitis are measurement of Epstein Barr virus (EBV) DNA in cerebrospinal fluid (CSF) and FDG-PET scan of the brain. EBV is often found in the CSF of people with PCNSL. The study also will compare the accuracy of two imaging techniques-TI-SPECT and FDG-PET-in distinguishing between toxoplasmosis and PCNSL. Patients 18 years of age and older who have HIV infection and at least one focal brain lesion without a prior history of PCNSL or toxoplasmic encephalitis may be eligible for this study. Each candidate is screened with a medical history, physical examination, blood and urine tests and MRI scans of the brain. Upon entering the study, all participants take medication to treat toxoplasmic encephalitis. They undergo lumbar puncture (spinal tap) to obtain CSF for analysis, an FDG-PET scan, and a 201TI-SPECT scan. For the PET scan, a radioactive substance is injected into an arm, followed by scanning in a doughnut-shaped machine similar to a CT scanner. SPECT is similar to PET but uses a different radioactive tracer, and the patient lies on a table while the SPECT camera rotates around the patient's head. Patients whose test results indicate a low risk for lymphoma continue antibiotic therapy for toxoplasmosis. They have repeat MRI scans around 4, 7, and 14 days after starting the drug to monitor the response to therapy. Antiretroviral therapy is initiated in patients who are not already on such a regimen. Patients whose test results indicate a high risk for PCNSL have a CT scan to look for evidence of lymphoma elsewhere in the body and are referred for consultation with a neurosurgeon to discuss undergoing a brain biopsy. The brain biopsy is done in the operating room under general anesthesia. A small cut is made in the scalp and a small opening is made in the skull over the area of the brain to be biopsied. A needle is placed in the opening in the skull and, guided by CT or MRI, moved to the abnormal area of the brain, where a small piece of tissue is removed for study under a microscope. Patients found to have toxoplasmosis are discharged from the hospital to the care of their primary care physician after they are getting better and are tolerating all their medications. They return to NIH for follow-up visits about 4 weeks, and 6 months after discharge. Patients found to have lymphoma are referred to the National Cancer Institute for screening for enrollment in a treatment protocol. Patients who are not eligible for a treatment protocol are referred back to their primary care physician or for another NIH treatment protocol, if one is available. Patients with lymphoma are seen at the NIAID outpatient clinic for follow-up visits and laboratory examinations every 3 months for 2 years.

This study aims at describing survival rates over time (Kaplan-Meier estimator) in patients suffering from AIDS-related primary central nervous system lymphoma who were diagnosed from 1996 to 2014 and treated with infusions of high-dose methotrexate and combined antiretroviral therapy.

The primary objective of this protocol is to provide expanded access to tabelecleucel to participants with Epstein-Barr virus-associated diseases and malignancies for whom there are no other appropriate therapeutic options, and who are not eligible to enroll in clinical studies designed to support the development and registration of tabelecleucel.