Study of Immune Responses and Safety of Recombinant CD40 Ligand in Patients With X-Linked Hyper IgM Syndrome
Bacteriophage
+ rhuCD40L
+ KLH
Immunologic Deficiency Syndromes+3
+ Immune System Diseases
+ Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Treatment Study
Summary
Study start date: October 1, 1999
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.5 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
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
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, United StatesOpen National Institute of Allergy and Infectious Diseases (NIAID) in Google Maps