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

Phase 2
Not Enrolling
Immunoproliferative Disorder

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Trial Information

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

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.

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.


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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

October 1999

Completion Date:

October 2003

Related Keywords:

  • Immunoproliferative Disorder
  • Primary Immunodeficiency
  • Gamma Globulin (IgG) Immunization
  • KLH
  • Phi-X 174
  • X-linked HyperIgM Syndrome
  • Immunoproliferative Disorders
  • Hyper-IgM Immunodeficiency Syndrome
  • Hyper-IgM Immunodeficiency Syndrome, Type 1



National Institute of Allergy and Infectious Diseases (NIAID) Bethesda, Maryland  20892