Study of Immune Responses and Safety of Recombinant Human CD40 Ligand in Patients With X-Linked Hyper-IgM Syndrome

NCT00001145 | Completed Phase 2

• 2 other identifiers: 00000600-I-0006
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Immunoproliferative Disorder

Keywords

Primary Immunodeficiency; Gamma Globulin (IgG) Immunization; KLH; Phi-X 174; X-linked HyperIgM Syndrome

Interventions

Bacteriophage DRUG

rhuCD40L DRUG

KLH DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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. doi: 10.1016/0167-5699(93)90188-Q.

  PMID: 7506037 BACKGROUND

• Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3(2):101-21.

  PMID: 1554497 BACKGROUND

• 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. doi: 10.1073/pnas.90.6.2170.

  PMID: 7681587 BACKGROUND

MeSH Terms

Conditions

Immunoproliferative Disorders; Primary Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

Immune System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: October 1, 1999
• Study Completion: October 1, 2003
• Last Updated: March 4, 2008

Record last verified: 2003-10

Locations

US (1)