Study of Immune Responses and Safety of Recombinant CD40 Ligand in Patients With X-Linked Hyper IgM Syndrome
Bacteriophage
+ rhuCD40L
+ KLH
Syndromes de Déficience Immunologique+3
+ Maladies du Système Immunitaire
+ Maladies et anomalies congénitales, héréditaires et néonatales
Étude thérapeutique
Résumé
Date de début de l'étude : 1 octobre 1999
Date à laquelle le premier participant a commencé l'étude.The purpose of this Phase I/II study is to evaluate clinical response and safety following administration of recombinant human CD40 ligand (rhuCD40L) in up to 5 patients with X-linked hyper IgM syndrome (XHIM). XHIM is a rare genetic disease caused by mutations in the gene encoding CD40 ligand (CD154) and is characterized by hypogammaglobulinemia, opportunistic infections, and an increased risk of neoplastic disease. Despite treatment with intravenous gamma globulin, the expected survival of patients with XHIM is less than 20% by the age of 25. The proposed protocol is a proof of principle study designed to determine if administration of rhuCD40L can reverse the core immunologic defects of patients with XHIM. To this end, we will immunize patients with neo antigens, specifically keyhole limpet hemocyanin (KLH) and Bacteriophage Phi-X 174 (PhiX174) to evaluate antigen-specific B and T cell responses. Clinical response and toxicity will be evaluated using routine hematological and clinical evaluation, quantitation of KLH and PhiX174 specific IgG in serum, measurement of proliferation and cytokine production to KLH simulation in vitro, and FACS analysis to quantitate memory B and T cells. Our long-term goal is to define a therapeutic regimen that will provide effective immunological reconstitution to patients with XHIM and improve life expectancy.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.5 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
INCLUSION CRITERIA: All patients must have a diagnosis of X-linked hyper IgM syndrome confirmed either by molecular analysis of the CD40L gene or by flow cytometry analysis demonstrating the failure of CD40L expression on activated T cells, and/or clear X-linked inheritance (with multiple affected males) in association with defective CD40L expression. Age greater than or equal to 4 years Patient and or parent (for children under the age of 18) must be able to understand and sign informed consent. Life expectancy of greater than 6 months. Average ANC of greater than 250 cells/microL measured over 3 days during the week prior to planned administration of rhuCD40L. EXCLUSION CRITERIA: Serious ongoing opportunistic infection. Use of immune-based therapies other than IVIG such as corticosteroids (doses of prednisone greater than 0.4 mg/kg/d for more than 4 weeks within the 6 months prior to enrolling in the study or any use of corticosteroids equivalent to greater than or equal to 5 mg of prednisone at the time of enrollment) or other immunomodulating drugs within 6 months prior to enrollment in the study. Current use of other investigational drugs. Chronic liver disease or any confounding medical illness that in the judgement of the investigators would pose added risk for study participants (e.g. cancer, severe allergies, chronic renal or pulmonary disease). SGOT, SGPT greater than 2 times normal range; and creatinine greater than 2.0 times normal ANC less than 250/microL; Platelets less than 50,000/microL; Hematocrit less than 25
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, United StatesOuvrir National Institute of Allergy and Infectious Diseases (NIAID) dans Google Maps