18 Clinical Trials for Various Conditions
The purpose of this study is to find out whether the study drug mogamulizumab is effective in preventing the development of adult T-cell leukemia/lymphoma (ATL) in people who are at higher risk for this type of cancer because they are infected with the HTLV-1 virus and because of changes seen in some of their immune system cells called T-cells.
Background: HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare, progressive disease. It occurs in some people infected with the HTLV-1 virus. It leads to weakness in the lower limbs and other serious problems. It has no treatment. Teriflunomide is a drug used to treat multiple sclerosis. It reduces immune cells that make the disease worse. Researchers want to learn if this drug can help people with HAM/TSP. Objective: To learn the effects, immune response, safety, and tolerability of teriflunomide in people with HAM/TSP. Eligibility: Adults ages 18 and older with HAM/TSP. Design: Participants will be screened under protocol 98-N-0047. Participants will have a medical history. They will have physical and neurological exams. They will have blood and urine tests. Participants will take 1 tablet of the study drug once a day for 9 months. They will keep a drug diary. Participants will have lymphapheresis. For this, blood is drawn from a needle in one arm. A machine divides the blood into red cells, plasma, and white cells. The white cells are removed. The plasma and red cells are returned to the participant through a needle in the other arm. Participants will have lumbar punctures ( spinal taps ). For this, a thin needle is inserted into the spinal canal in the lower back. Spinal fluid is removed. Participants will have magnetic resonance imaging (MRI) of the brain and spine. The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI, participants will lie on a table that can slide in and out of the scanner. Participation will last for 15 months.
This is a research study for subjects who have been diagnosed with Adult T cell Leukemia/Lymphoma, a rare and aggressive peripheral T cell neoplasm caused by the virus HTLV1. Currently, there is no accepted standard therapy for this disease. The purpose of this research study is to evaluate the use of the investigational drug lenalidomide in the treatment of Adult T cell Leukemia/Lymphoma. Lenalidomide is a drug that alters the immune system and it may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for patients with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM are cancers of the blood. It is currently being tested in a variety of cancer conditions. In this case it is considered experimental.
This study will identify chemical and protein markers in the blood of people who carry the human T-lymphotropic virus type I (HTLV-I), a virus associated with various pathologies, including an increased risk in adults of a rare and aggressive cancer called adult T cell leukemia/lymphoma (ATL). The study will also examine differences in these markers before and after the onset of ATL. ATL has been reported in every area where HTLV-1 is common, including the Caribbean and parts of Japan, West Africa, the Middle East, South America, and Pacific Melanesia. Risk factors for the disease are largely unknown and seem to vary among those affected in different endemic regions. People who acquire the infection early in life are thought to be at higher risk than those who are infected later. In Japan, men seem to be at greater risk than women, but the same is not evident among the black population in the Caribbean and Brazil. Findings from this study will increase understanding of the cause of ATL and identify differences in tumor characteristics and the course of disease across geographical areas. Study subjects are drawn from among participants in eight studies of HTLV-1 carriers, including the 1) Jamaica Mother-Infant Cohort Study, 2) Jamaica Family Study, 3) Jamaica Food Handlers Study, 4) Miyazaki Cohort Study in Japan, 5) Nagasaki Cohort Study in Japan, 6) Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Disease, 7) HTLV Outcome Studies in the United States, and 8) GIPH Cohort Study in Brazil. Stored blood samples previously collected from patients in the above studies who did and did not develop ATL will be analyzed for immunologic and genetic factors.
This study will examine the use of the humanized Mik-Beta-1 (Hu Mik-(SqrRoot) 1) monoclonal antibody in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Some patients infected with the human T-lymphotropic virus type 1 (HTLV-1) virus develop HAM/TSP, a disease in which the immune response to HTLV-1 becomes directed against the person's own body in what is called an autoimmune response. Hu-Mik-Beta-1 is a genetically engineered antibody that blocks the action of a chemical produced by the body during infection or inflammation called interleukin 15 (IL-15). Blocking IL-15 may prevent the autoimmune response that results in HAM/TSP. Patients 18 years of age and older with HAM/TSP may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, and an electrocardiogram. Participants undergo the following procedures: 1. Baseline visit(s): Repeat physical examination and blood and urine tests, as well as the following: * Lumbar puncture: A local anesthetic is injected to numb the skin of the lower back. A needle is inserted in the space between the bones where the cerebrospinal fluid that bathes the brain and spinal cord circulates below the spinal cord. About 4 tablespoons of fluid is collected through the needle. * Magnetic resonance imaging (MRI): This test uses radio waves and magnets to produce images of body tissues and organs. The patient lies on a table that slides into a metal cylinder surrounded by a strong magnetic field. During part of the scan, a contrast agent is injected to brighten the images. * Apheresis: This procedure is used to collect large quantities of white blood cells. Whole blood is collected through a needle in an arm vein and directed into a machine that separates it into its components by spinning. The white cells and plasma are removed and the rest of the blood (red cells and platelets) is returned to the body through the same needle. 2. Hu Mik-Beta-1 treatment: Infusions of Hu Mik-Beta-1 are given through a vein every 3 weeks for nine doses. The first treatment requires at least an overnight hospital stay; subsequent infusions are given in the outpatient clinic. 3. Blood and urine tests and a physical examination at every treatment visit and a skin test at one treatment visit. 4. Research tests at the end of the 24-week treatment period, including lumbar puncture (spinal tap), MRI scan, and apheresis. 5. After completing treatment, patients have three follow-up clinic visits for blood and urine tests, and a skin test at one follow-up visit.
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Antiviral therapy may kill viruses such as HTLV-1 that can cause cancer. Interferon alfa may interfere with the growth of cancer cells. Combining chemotherapy with antiviral drugs and interferon alfa may be effective in treating adult T-cell leukemia/lymphoma. PURPOSE: Phase II trial to determine the effectiveness of combination chemotherapy followed by antiviral therapy and interferon alfa in treating patients who have adult T-cell leukemia/lymphoma caused by HTLV-1.
This study will use three different magnetic resonance imaging (MRI) techniques to study HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/STP)-a disease of slowly progressive weakness in the legs. It is not known how the HTLV-1 virus causes this disease, but it is thought that as the body's immune system tries to destroy the virus, parts of the nervous system-primarily the spinal cord-are damaged. Patients 18 years of age and older with HAM/TSP and healthy normal volunteers may be eligible for this study. Participants will undergo diffusion tensor MRI, MR-spectroscopy, and magnetization transfer imaging to look at different compositional, architectural, and microscopic properties of the brain. All of these techniques are similar to conventional MRI, and like the conventional method they use a strong magnetic field and radio waves to measure structural and chemical changes in brain tissue. Each of the three scans will be done on separate days, each lasting about 1 hour. For the procedures, the patient or volunteer lies on a stretcher in a narrow metal cylinder (the scanner) and is asked to remain still for 15 to 30 minutes at a time. A special lightweight coil may be placed on the head to enhance the brain images. The subject can communicate with the person doing the scan at all times.
HTLV stands for human T cell leukemia virus. HTLV-1 is a virus that attacks specific kinds of white blood cells called T cells. T cells are part of the natural defense system of the body. HTLV-1 has been associated with leukemia and lymphoma. In addition, approximately 1% of all patients infected with HTLV-1 develops a condition known as HTLV-1 associated myelopathy (HAM) / tropical spastic paraparesis (TSP). Currently there is no clearly defined, effective treatment for patients with HAM/TSP. Steroids have been used as therapy but have only been able to provide temporary relief of symptoms. Human interferon is a small protein released from different kinds of cells in the body. Interferon has been known to have antiviral and immunological effects and has been used to treat hepatitis and multiple sclerosis. Interferon Beta is released from cells called fibroblasts. These cells play a role in the production of connective tissue. The purpose of this study is to evaluate the possible role of recombinant interferon beta (Avonex) in treatment of HAM/TSP. The study is broken into three phases, a pre-treatment phase, a treatment phase, and a post-treatment phase. The total duration of the study will be 44 weeks. Patients participating in this study will receive injections of Avonex 1 to 2 times a week. Throughout the study patients will regularly submit blood samples and undergo diagnostic tests such as MRI and measures of somatosensory evoked potentials.
This phase I trial studies the side effects and best dose of lenalidomide when given together with usual combination chemotherapy (etoposide, prednisone, vincristine sulfate \[Oncovin\], cyclophosphamide, and doxorubicin hydrochloride \[hydroxydaunorubicin hydrochloride\], or "EPOCH") in treating adult T-cell leukemia-lymphoma. Lenalidomide may help shrink or slow the growth of adult T-cell leukemia-lymphoma. Drugs used in chemotherapy, such as etoposide, vincristine, cyclophosphamide, and doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving lenalidomide and the usual combination chemotherapy may work better in treating adult T-cell leukemia-lymphoma compared to the usual combination chemotherapy alone.
This phase II trial studies how well nivolumab works in treating patients with peripheral T-cell lymphoma that has come back after a period of improvement or that does not respond to treatment. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells.
This phase II trial studies how well nivolumab works in treating patients with human T-cell leukemia virus (HTLV)-associated T-cell leukemia/lymphoma. Nivolumab is an antibody, which is a type of blood protein that tags infected cells and other harmful agents. Nivolumab works against a protein called programmed cell death (PD)-1 and may help the body destroy cancer cells by helping the immune system to keep fighting cancer.
Background: - Human T-cell lymphotropic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an infection of the spinal cord. The infection is caused by a virus that has been known to cause cancers like leukemia and lymphoma. It causes a weakening of the legs. Researchers want to see if raltegravir, a drug for treating human immunodeficiency virus (HIV), can be used to treat HAM/TSP. They will see if the drug can reduce the amount of virus in the blood of people with HAM/TSP. Objectives: - To see if raltegravir can reduce the viral load of people with HAM/TSP. Eligibility: - Individuals at least 18 years of age who have HAM/TSP. Design: * Participants will be screened with a physical exam and medical history. Blood samples will be collected. Imaging studies will be performed. A lumbar puncture will also be taken. * Participants will take the study drug twice a day for 6 months. They will note each dose in a study diary, as well as any side effects. * At the 6-month visit, participants will stop taking the study drug. They will have a physical exam and blood samples, as well as other tests. * Participants will have two further exams 9 months and 15 months after starting the study drug. They will have a physical exam and blood samples, as well as other tests.
Background: * The human T-cell leukemia virus 1 (HTLV-1) causes adult T-cell leukemia (ATL). Infection does not immediately cause ATL, but it can develop over time. ATL is a rare and aggressive type of cancer that disrupts the body's ability to control the HTLV-1 virus. Infected T lymphocytes that are transformed by HTLV-1 into malignant ATL cell have constitutively activated Interleukin-2 (IL-2), IL-9 and IL-15 production pathways that function as autocrine and paracrine stimulators of these cells by stimulating these cells through the Janus Kinase (JAK) 1 and 3/Signal transducer and activator of transcription 5 (STAT5) pathways. * Ruxolitinib is a drug that has been approved to treat bone marrow disorders. Ruxolitinib is a tyrosine kinase inhibitor that disrupts signaling through the JAK 1 and 2/STAT3 and 5 pathways and have potential as a treatment for ATL. Researchers want to see if ruxolitinib can be a safe and effective treatment for ATL. * Initially this trial was designed as a single dose level phase II trial with ruxolitinib given at the dose approved for the treatment of primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. * Clinical and correlative laboratory data demonstrated limited inhibition and impact on the subject's disease with the standard 20 mg twice daily dose. Given that the manufacturers of ruxolitinib had safety data for administering ruxolitinib to normal healthy volunteers at doses up to 50 mg twice or 100 mg once daily, the trial was reconfigured as a phase I dose escalation trial giving these higher doses on the twice daily schedule Objectives: Initial Phase II design: * Define clinical or objective response rate for the 20 mg twice daily dose of Ruxolitinib. * Define safety profile, Time to progression and survival time. Subsequent Phase I dose escalation with expansion cohort treated at the MTD or MAD: * Determine the maximum tolerated dose (MTD) and clinical response rate for ruxolitinib administered at the higher dose levels. * Determine safety profile, time to progression * To test the safety and effectiveness of ruxolitinib for adult T-cell leukemia. Eligibility: - Individuals at least 18 years of age who have ATL caused by HTLV-1. Design: * Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will also be performed. * Participants will take ruxolitinib twice a day for 28 days. They will have blood tests on days 1, 14, and 28. These tests will look at the levels of HTLV-1 in the blood. Participants will have a final blood test about 2 weeks later. Treatment will also be monitored with imaging studies. * Participants who have a partial response during treatment may be able to start taking ruxolitinib again after the final blood test. They will continue to take ruxolitinib for as long as it is effective and the side effects are not severe. * Participants who have a full response during treatment will take ruxolitinib for 56 more days, and then stop treatment. If ATL returns, they may restart treatment and continue it for as long as it is effective.
RATIONALE: Human T-cell lymphotropic virus type 1 (HTLV-1) can cause cancer. Zidovudine is an antiviral drug that acts against the human T-cell lymphotropic virus type 1. Giving zidovudine, interferon alfa-2b, and PEG-interferon alfa-2b together may stimulate the immune system and slow down or keep the cancer cell from growing. PURPOSE: This clinical trial is studying how well giving zidovudine together with interferon alfa-2b and PEG-interferon alfa-2b works in treating patients with human T-cell lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma.
This study is for patients with lymphoproliferative malignancies that have progressed after receiving a previous treatment (relapsed) or are no longer responding to treatment (refractory). To be in this study, patients must have certain types of Hodgkin's lymphoma (HL), peripheral T-cell lymphoma (PTCL), or B-cell lymphoma, including Waldenstrom's macroglobulinemia. This study is being done to find doses of the combination of pralatrexate and gemcitabine with vitamin B12 and folic acid that can be safely given to patients with these types of lymphoma and explore the effectiveness of the treatment.
This study will examine the safety and effectiveness of Alemtuzumab (Campath-1H) for treating patients with adult T-cell leukemia/lymphoma (ATL). ATL is caused by a virus called human T-cell lymphotrophic virus type-1 (HTLV-1) that infects lymphocytes (white blood cells) called T-cells. Cancerous cells can be found not only in the blood, but also in the skin, lungs, lymph nodes, liver, bone, bone marrow, spleen, and meninges (tissues covering the brain). There are four categories of ATL, based on the aggressiveness of disease-smoldering, chronic, lymphoma, and acute. Campath-1H is a monoclonal antibody that attaches to and kills normal and cancerous lymphocytes, including T cells. Although Campath-1H is an experimental drug for treating ATL, it is approved by the Food and Drug Administration for treating chronic lymphocytic leukemia. Patients 18 years of age and older with any type of ATL except smoldering may be eligible for this study. Candidates are screened with a medical history and physical examination, photos of skin lesions, measurement of lesions such as lymph nodes and skin nodules, blood and urine tests, electrocardiogram (EKG), chest x-ray, computed tomography (CT) scan or ultrasound of the abdomen, skin biopsy, bone marrow aspirate and biopsy, skin test, and lumbar puncture (spinal tap). Participants undergo treatment in two phases, as follows: * Dose escalation phase: Patients receive an infusion of Campath-1H daily for three days. The initial dose is low and is increased daily as long as there are no side effects, or only mild reactions, until the patient is receiving the maximum dose of 30 milligrams per day. * Stable dose phase: Patients receive infusions of Campath-1H 30 mg three times a week for up to 12 weeks. In addition to treatment, patients are evaluated with the following tests and procedures: * History and physical examination every 4 weeks. * Blood tests every 4 weeks. * CT scans to measure the size of the tumors every 4 weeks. * Skin biopsies (if skin disease is present) and lymph note aspirates: Up to five biopsies and five aspirates may be taken to help diagnose the disease and evaluate the effect of Campath-1H on the cancer. * Bone marrow biopsy: This procedure may be done to document or monitor disease progress. Patients receive treatment for up to 12 weeks. Treatment may stop earlier if the patient achieves a complete response before the end of 12 weeks. Patients completing the study are followed periodically with a history and physical examination, blood and urine tests, tumor evaluation, skin biopsy and skin testing. They are seen monthly at first and then at 3-month intervals the first year; every 4 months the second year, every 6 months for the third through fifth years, and then yearly.
Objective: Human T-lymphotropic virus type-I-associated myelopathy / tropical spastic paraparesis (HAM/TSP) is a rare neurologic disorder that affects less than 5% of patients infected with the HTLV-I virus. The purpose of this protocol is to study the natural history of HAM/TSP by monitoring clinical progression of patients longitudinally. Additionally, we will attempt to define the virological and immunological changes of HAM/TSP. Study Population: Patients with HAM/TSP who fulfill World Health Organization diagnostic criteria are eligible to participate in this protocol. Asymptomatic seropositive individuals and individuals with indeterminate HTLV-1 serology are also eligible to participate. Design and Outcome Measures: A longitudinal assessment of clinical, virological and immunological progression in HAM/TSP will be accomplished through periodic testing and evaluation. Asymptomatic seropositive individuals, those with seroindeterminate HTLV-I serology and normal volunteers may serve as controls. Longitudinal standardized neurological examinations will be performed. Longitudinal samples of serum, plasma, and lymphocytes may be obtained from participants. Lumbar punctures may be performed on all participants. These samples will be used virological and immunological assays. A focus is on the relationships between the characteristics of viral infection, the immune response, and the genetic makeup.
Adult T-cell leukemia (ATL) is and aggressive characterized by the presence of cluster of differentiation 4 (CD4)/cluster of differentiation 25 (CD25)-expressing T cells (interleukin-2 \[IL-2\]R expressing) in the peripheral blood and in lymphoid and other tissues. Denileukin diftitox (Ontak(Registered Trademark)) is a genetically engineered fusion protein that targets IL-2-expressing malignancies. Denileukin diftitox interacts with the IL-2R on the cell surface, is internalized via endocytosis, and inhibits cellular protein synthesis, resulting in cell death within hours to days. The objectives of this study are to determine the clinical response to Denileukin diftitox of patients with adult T-cell leukemia (ATL) and the safety of Denileukin diftitox in those patients. Eligible participants must be 18 years of age or older with chronic, lymphomatous and acute forms of ATL, and must be infected with human T-cell lymphotropic virus type I (HTLV1). Patients will be treated with 9 mcg/kg/d of Denileukin diftitox intravenously for 5 days every 2 weeks. Tumor response will be evaluated after two cycles of treatment. Stable or responding patients will continue treatment for a total of 12 months, with evaluations every four cycles of treatment. Patients will be treated for two cycles beyond a complete remission. The trial uses an optimal two-stage design targeting for a true response proportion of more than 30 percent. Nine patients will be treated initially, with expansion to 29 patients if a response is seen in 1 of the initial 9 patients treated. Treatment will be discontinued if a patient experiences serious side effects. A potential benefit is that a patient may undergo partial or complete remission. The research may not directly benefit participants, but the results may aid in the treatment of others.