Immunoproliferative Disorder Clinical Trial
Official title:
Study of Immune Responses and Safety of Recombinant CD40 Ligand in Patients With X-Linked Hyper IgM Syndrome
The primary goal of this Phase I/II study is to assess the immune response and safety of
recombinant human CD40 ligand (rhuCD40L) in patients with X-linked hyper IgM syndrome
(XHIM). XHIM is a rare genetic disease caused by mutations in the gene encoding CD40 ligand.
Individuals with this syndrome fail to make gamma immune globulin, frequently suffer from
opportunistic infections, and are at an increased risk of developing cancer. Despite
treatment with gamma globulin replacement therapy, the expected survival of patients with
XHIM is less than 20 percent by the age of 25.
In a mouse model of this syndrome, treatment with man-made CD40 ligand protein protected the
mouse from opportunistic infections, restored the mouse's ability to make gamma globulin,
and improved survival. We want to determine if a similar approach can work in humans with
XHIM. The study will be conducted at the Clinical Center of the National Institutes of
Health in Bethesda, Maryland.
For most patients, rhuCD40L will be administered by injection under the skin over a period
of six months and follow-up exams are required at 2-month intervals for an additional 6
months. During the study, patients will be maintained on intravenous gamma globulin,
antibiotics to protect against opportunistic infection, and, if needed, growth factors to
control neutropenia. The immune response to rhuCD40Lwill be measured by routine methods such
as measuring a patient's ability to synthesize gamma globulin when challenged with
immunizations to keyhole limpet hemocyanin (KLH) and Bacteriophage Phi-X 174 (Phi-X 174).
Our long-term goal is to define a therapeutic regimen that will provide effective
immunological reconstitution to patients with XHIM and improve their life expectancy.
| Status | Completed |
| Enrollment | 5 |
| Est. completion date | October 2003 |
| Est. primary completion date | |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | N/A and older |
| Eligibility |
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 |
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institute of Allergy and Infectious Diseases (NIAID) | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Callard RE, Armitage RJ, Fanslow WC, Spriggs MK. CD40 ligand and its role in X-linked hyper-IgM syndrome. Immunol Today. 1993 Nov;14(11):559-64. Review. — View Citation
Fuleihan R, Ramesh N, Loh R, Jabara H, Rosen RS, Chatila T, Fu SM, Stamenkovic I, Geha RS. Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2170-3. — View Citation
Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3(2):101-21. Review. — View Citation