View clinical trials related to Immunologic Deficiency Syndromes.
Filter by:Patients enrolled in NIH protocol 95-I-0133 at the Clinical Center may participate in an extension phase of this study in which the drug prednisone will be eliminated from the treatment regimen. Prednisone is associated with avascular necrosis, a condition that has been found in a number of patients in this study. Also, certain patients in this protocol may receive future interleukin-2 treatment cycles at home. Home administration of IL-2 injections involves less frequent data and safety monitoring and no medical evaluations at the Clinical Center except at the beginning of each cycle. To be eligible for home administration of IL-2, patients must: - Be enrolled in a current NIAID protocol for IL-2 therapy and have received at least 1 year of treatment on the protocol, with at least two well-tolerated outpatient cycles at a stable dose. - Have a history of tolerable side effects while receiving IL-2 without frequent medical interventions, intravenous fluid replacement or dose reductions. - Not have had any significant clinical or laboratory abnormalities during days 0 to 5 of the last two outpatient cycles. - Have a strong relationship with a private physician or health-care provider who has been involved in the patient's care and is willing to help supervise the patient's care during each home IL-2 cycle. - Live in a home with easy telephone access and have proved reliable in responding to telephone calls from clinic staff. - Give the clinic staff contact information for a close friend or relative who will agree to serve as a caregiver during each home cycle, providing the patient non-medical assistance and checking on his or her condition daily. - Have reasonable access to emergency medical services and a nearby medical facility. - Have proved reliable and consistent in using sterile technique, reconstituting IL-2 vials and administering subcutaneous IL-2 injections. - Be receiving outpatient IL-2 injections cycles at least once every 6 months as part of their normal protocol participation. - Have access to a home weight scale and be able to weigh themselves each day for safety monitoring. Participants will receive IL-2 cycles on the same schedule they followed in their original protocol participation. They will be seen at the Clinical Center at regularly scheduled follow-up visits between cycles and for a medical evaluation and blood drawing before the start of each cycle to determine the safety of administering the cycle. During the home cycle, the patient's case manager or other team member will place monitoring telephone calls on days 2 and 4 of the cycle and again a week later. The timing and number of these calls may change depending on the findings of ongoing assessments of their usefulness. Patients will be required to notify the study team promptly of any complications or other problems that develop with therapy.
The purposes of this study are to 1) identify the genes responsible for certain immune disorders, 2) learn about the medical problems they cause, and 3) learn how to predict who is likely to develop these disorders and what the risk is of passing them on to children. The immune system is the body s defense system. Some immune deficiencies impair a person s ability to fight infections; others render a person susceptible to allergies, or to autoimmune diseases such as lupus or arthritis, in which the immune cells (white blood cells) attack and destroy the body s own tissues. Patients with immune disorders known or suspected to have a genetic basis and their family members may enroll in this study. Eligibility will be determined by a review of the patient s medical records and family medical history. Participants will provide a small blood sample for genetic (DNA) and white blood cell analysis. Gene samples (but not white blood cells) may also be obtained by mouth brushing or skin biopsy. For the mouth brushing, a small brush is rubbed against the inside of the cheeks for 1 minute to wipe off some cells. For the skin biopsy, a small circle of skin (about 1/8 inch) is removed under local anesthetic. Pregnant women may be asked to provide a fetal sample (amniotic fluid cells or chorionic villus sample). All samples will be used for immune or genetic studies of the family s immune disorder. If test results show a specific genetic variation responsible for the family s immune disorder, a report will be sent to the patient s doctor or genetic counselor, who will discuss the implications for the family. NIH researchers and genetic counselors will also be available to explain results and answer questions. Information will not be available in the case of disorders that cannot yet be linked to a specific genetic abnormality. Information from this study will increase knowledge about the immune system and what causes immune deficiencies. Participants may also learn the underlying cause of an immune disorder that affects them or someone in their family information may be useful in guiding treatment and in making decisions regarding family planning.
This is a phase I/II study to determine the safety and tolerance of the protease inhibitor indinavir (MK-0639), alone and then in combination with HIV reverse transcriptase inhibitor therapy in children with HIV infection. Indinavir sulfate (the capsule formulation) has been shown to have potent antiviral activity and an acceptable safety profile in adults. HIV-infected children who have not received prior antiretroviral therapy, and children who have become refractory to prior therapy, or who have experienced toxicity to prior therapy, will be included. In addition, we will explore viral and CD4 cell kinetics before starting therapy and following exposure to antiretroviral agents. The study will be conducted in three parts. 1. In order to help interpret the antiviral activity of indinavir, the virologic and immunologic profile of children will be studied within 2 weeks prior to starting the therapeutic part. For children who have never been treated, this will be before the initiation of any antiretroviral therapy and for children who have already received antiretroviral therapy, this will be done during the initial "wash-out" phase that is routinely interposed between two different treatment regimens. 2. The initial 16 weeks of therapy will then evaluate the toxicities, pharmacokinetics, and preliminary efficacy of single drug therapy with indinavir. 3. Subsequently, all children who are able to tolerate the combination of zidovudine and lamivudine (i.e., have no prior history of intolerance to one of these two agents) will be treated with these two reverse transcriptase inhibitors in addition to the protease inhibitor indinavir. Zidovudine and lamivudine will be added after 16 weeks at a fixed dosage. Toxicity, pharmacokinetics, and preliminary efficacy of indinavir will also be investigated after combination therapy. All patients who wish to remain in this study after 96 weeks of therapy and who do not meet off study criteria will be permitted to receive extended treatment with their current indinavir combination therapy for an additional 48 weeks. The study will determine the pharmacokinetic profile of indinavir, given as single drug or in combination with zidovudine and lamivudine. It will assess the preliminary antiviral and clinical activity by monitoring clinical status, viral burden in plasma, and markers of immunologic status. Based on safety and preliminary efficacy results from studies performed in adults, we will study three dose levels which are expected to result in drug levels above the IC95 of HIV-1 for all or most of the dosing interval.
Patients with congenital or acquired immunodeficiencies are at an increased risk to develop polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative disorder that can follow a clinically aggressive course and may represent a pre-malignant lesion. Although most of these lymphoproliferative disorders are of B-cell origin, T-cell or non-B-non-T-cell processes have also been observed. The pathogenesis is only partially understood. In the case of pre-malignant conditions it is often difficult to know when and whether a therapeutic intervention is necessary and a careful consideration of potential treatment-associated morbidity is indicated. Therapies have ranged from influencing the possible infectious etiology (by treating with acyclovir), decreasing the amount of immunosuppression (in transplant patients), to the use of immunomodulatory agents, including interferons and interleukins. Recent data have indicated that the use of differentiating agents, such as the retinoids, might offer yet another treatment option. In the current study we will try to get a better understanding of the pathogenesis and natural course of lymphoproliferative disorders in immunodeficient children. The study will have two parts: an initial observation period to obtain information on the natural course of these disorders, and then a six month treatment period with the combination of a differentiating agent (13-cis-retinoic acid was used until all-trans-retinoic acid became available on 7/96) with an immunomodulatory agent (interferon-alpha2a, IFN-alpha2a).
Children and adolescents with HIV/AIDS are living well beyond life expectancy that was projected for them in the recent past. Little is known about the psychosocial variables that coincide with long-term survival of HIV/AIDS. This longitudinal study examines the psychosocial factors and adaptive coping strategies associated with long-term survival of HIV/AIDS in children and how these factors change over a period of two years. In addition, data is being collected from the primary caretakers on their own psychological well-being as will as their perceptions of their child's adjustment and coping. Participants include children who have been infected (either perinatally or through transfusion) for at least eight years and who were aware of their diagnosis.
Patients enrolled in this study will not receive investigational therapy. Any treatments rendered will be standard and based on appropriate medical care. Should a patient become eligible for an experimental therapy protocol, the normal process of enrollment and informed consent will be followed.
Certain patients enrolled in NIH protocol 94-I-0206 at the Clinical Center may be eligible to participate in one or more of the following new options: - Donor/recipient extension phase - Both the recipient (HIV-infected twin) and donor (non-infected twin) will participate in this extension of the CD4-zeta gene therapy study. It will evaluate the safety and activity of infusing gene-modified CD4+ cells as well as the modified CD8+ cells. - Corticosteroid administration - A corticosteroid, such as prednisone, hydrocortisone or prednisolone, will be added to the interleukin-2 (IL-2) regimen for preventing or treating side effects of IL-2 such as fever and other flu-like symptoms. - Extended follow-up - A more intensive follow-up will be scheduled for patients with substantial numbers of lymphocytes that harbor the CD4-zeta gene. Every 3 months, participants will have blood tests and specialized tests of CD4 counts, HIV-1 viral load and numbers of circulating cells containing the CD4-zeta gene every 3 months> the frequency of follow-up visits may be reduced as time goes by. - IL-2 continuation - Participants will continue to receive periodic treatment with IL-2 to see how long the genetically modified cells persist in the bloodstream and to evaluate the long-term response to IL-2. - Home treatment with interleukin-2 - Participants may receive future IL-2 treatment cycles at home. Home treatment involves less frequent data and safety monitoring and no medical evaluations at the Clinical Center except at the beginning of each cycle.
Synthetic HIV Peptide Vaccines (Treatment Protocol) We are conducting a study to evaluate the safety of two peptide vaccines (given alone or in combination) in patients with early HIV infection. Patients entered onto the study must have >500 CD4 cells/mm(3) and have preserved cardiac, hepatic, renal, and bone marrow function. Patients must be off all anti-retroviral therapy for at least 6 months and may not have received any experimental HIV vaccines. The vaccines being testing in this trial are comprised of short peptide segments of the HIV envelope, including the V3 loop. In animal studies, the peptides were able to induce neutralizing antibodies as well as cytotoxic T responses to HIV. This will be the first trial in which they are given to humans. The study will last for approximately one year, during which time the volunteers will receive 6 peptide vaccines under the skin. For more information, please call Tino Merced-Galindez, R.N. at (301) 496-8959 or Dr. Richard Little at (800) 772-5464.
Certain patients who are participating in NIH protocols involving interleukin-2 (IL-2) therapy for HIV disease may be requested to have the following changes or additions to their study protocol: - 3-day subcutaneous (sc) IL-2 administration: Patients currently receiving IL-2 intravenously (injections through a vein) may switch to subcutaneous administration (injections under the skin). Injections are given twice a day for 3 to 5 days (one treatment cycle), with cycles repeated no more often than every 8 weeks. - Home treatment of sc IL-2: Home administration of IL-2 injections involves less frequent data and safety monitoring and no medical evaluations at the Clinical Center except at the beginning of each cycle. Participants will receive IL-2 cycles on the same schedule they followed in their original protocol. They will be seen at the Clinical Center at regularly scheduled follow-up visits between cycles and for a medical evaluation and blood drawing before the start of each cycle to determine the safety of administering the next cycle. During the home cycle, the patient's case manager or other team member will place monitoring telephone calls on days 2 and 4 of the cycle and again a week later. The timing and number of these calls may change depending on the findings of ongoing assessments of their usefulness. Patients will be required to notify the study team promptly of complications or other problems that develop with therapy. - Stored specimens and HLA testing: Stored blood and tissue samples from patients will be used for future research on HIV, AIDS and related medical conditions, and the immune system. The samples may be labeled with no identifying information, with identifying information, such as the patient's name, or with a code that only the study team can link to the patient. Some of the blood drawn may be used for HLA typing, a genetic test of markers of the immune system. Usually used to match bone marrow or organ transplants, HLA type might also be used to try to identify factors associated with the progression of HIV disease or related conditions. Determining HLA type is also necessary to be able to perform certain research studies. - Tonsillar biopsy: Examination of tonsil tissue may provide information on the effects of IL-2 on the immune system and the expression of HIV. Patients in the randomized IL-2 study (93-CC-0113) may have tonsillar biopsies done up to three times-soon after enrollment, after month 4, and after month 12. Patients in the open IL-2 study (91-CC-0143) would have procedures no more often than every 3 months, with the following exception: patients in either study who are willing to have repeat biopsies performed during IL-2 therapy will have the procedure done up to three times during a round of IL-2: before Il-2 therapy, day 2-3 or IL-2 therapy, and day 4-6 of IL-2 therapy, if the sequential biopsies can be safely performed. The area to be biopsied will be numbed with a local anesthetic and 1 to 2 small pieces of tissue will be biopsied. - Skin biopsy: Examination of skin tissue may help to explain how IL-2 causes changes in the skin. Biopsies will be obtained from areas of the skin that have been affected by IL-2 as well as from normal, unaffected areas for comparison. Patients with Kaposi sarcoma will also have biopsies of normal skin to allow comparison with IL-2-induced changes in the Kaposi sarcoma lesions. The areas to be biopsied will be numbed with local anesthetic and a 2-mm (1/10th-inch) piece of skin will be biopsied from each site.
This study will evaluate the safety of giving lymphocytes (white blood cells) containing a new gene to HIV-infected individuals and will determine how long the cells survive in the bloodstream. Although the genetically altered cells will not directly benefit participants, knowledge about the safety, side effects and survival of these gene-marked cells in HIV-infected patients may lead to new treatment strategies. Identical twin pairs 18 years of age and older-one infected with HIV, the other non-infected-may be eligible for this study. Candidates will be screened with a medical history, physical examination and blood tests. All participants will have a tetanus booster shot. Non-infected twins will undergo a procedure called apheresis to collect white blood cells. For this procedure, whole blood is collected through a needle in an arm vein, similar to donating blood. The blood is separated it into its components by centrifugation (spinning), the white cells are removed, and the rest of the blood is returned to the body, either through the same needle or through another needle in the other arm. The harvested white cells will be grown in culture for approximately 10 days to 2 weeks to increase their numbers up to 1000-fold. A gene called NeoR, which is derived from bacteria, will be inserted into the cells, and these gene-marked cells will be infused into the HIV-infected twin. HIV-infected twins will be admitted to the NIH Clinical Center for the first cell infusion. The gene-marked cells will be infused over a 60-minute period through a plastic tube (catheter) placed in an arm vein, or, if a suitable arm vein cannot be found, through a special catheter placed into a large vein in the neck or chest. Vital signs (temperature, pulse, blood pressure and breathing rate), blood oxygen concentration, and urine output will be monitored regularly for 24 hours. Blood samples will be collected before and after the infusion to monitor for gene-marked cells. Patients will be discharged the next day. They will return to NIH daily the first week (from Monday through Thursday) to monitor for CD4 cell counts, plasma viral burden, p24 antigen levels, HIV levels and the presence of the NeoR gene, and then weekly for the next 5 weeks for these tests and others to monitor blood and urine chemistry, blood counts and immune function markers. If the NeoR gene cannot be detected after the first cell infusion, the entire procedure (donor apheresis, gene marking and infusion of cells) will be repeated twice-about once every 6 weeks. If the first infusion was uncomplicated, the second and third infusions may be done on an outpatient basis, with monitoring for 6 hours rather than 24. Six weeks after the third infusion, tests will be scheduled monthly for 6 months and then yearly for long-term follow-up. In addition to the above procedures, patients with a baseline CD4 lymphocyte count less than 100 cells per cubic millimeter of blood will be asked to undergo apheresis periodically to obtain the most accurate results for determining how long the NeoR gene persists in the blood. The procedure will be done weekly for the first 6 weeks after each infusion of cells, then at week 8, and then every 4 weeks until the gene can no longer be detected in the lymphocytes. The schedule may change, but will not require more frequent apheresis.