Immunoproliferative DisorderPhase 2NCT00001145
Study of Immune Responses and Safety of Recombinant Human CD40 Ligand in Patients With X-Linked Hyper-IgM Syndrome
A Phase 2 study testing Bacteriophage, rhuCD40L and KLH in people with Immunoproliferative Disorder, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Immunoproliferative Disorder
- What is being tested?
- Bacteriophage, rhuCD40L and KLH
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 1999to Oct 2003
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
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.
Read the detailed description
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.
- Conditions
- Immunoproliferative Disorder
- Being tested
- Bacteriophage, rhuCD40L, KLH
- Keywords
- Primary Immunodeficiency, Gamma Globulin (IgG) Immunization, KLH, Phi-X 174, X-linked HyperIgM Syndrome
- Medical subject headings
- Immunoproliferative Disorders, Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BacteriophageDrug
rhuCD40LDrug
KLHDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startOct 1999
- Study completionOct 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Immunoproliferative DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 5 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001145
- Sponsor's protocol ID
- 000006
- Other IDs
- 00-I-0006
- Status last verified
- Oct 2003
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
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.
PubMed 7506037Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3(2):101-21.
PubMed 1554497Fuleihan 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.
PubMed 7681587
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Immune Responses and Safety of Recombinant CD40 Ligand in Patients With X-Linked Hyper IgM Syndrome
- ClinicalTrials.gov ID
- NCT00001145
- Acronym / sponsor ID
- 000006
- Conditions
- Immunoproliferative Disorder
- Keywords
- Primary Immunodeficiency, Gamma Globulin (IgG) Immunization, KLH, Phi-X 174, X-linked HyperIgM Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Oct 1999
- Study completion
- Oct 2003
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bacteriophage | Drug | – |
| rhuCD40L | Drug | – |
| KLH | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 7506037Callard 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.
- Background: PubMed 1554497Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3(2):101-21.
- Background: PubMed 7681587Fuleihan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bacteriophage, rhuCD40L and KLH in people with Immunoproliferative Disorder, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001145, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.