Treatment of Adult-Onset Immunodeficiency With Bortezomib

Study Overview
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Brief Summary
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This is pilot study aimed to investigate the application of proteosome inhibitor, Bortezomib in treatment of patients with neutralizing autoantibody to IFN-γ. The investigators hypothesis is that bortezomib will reduce the antibody level and restore interferon-gamma function, resulting in clinical improvement and should be well-tolerated and safe for use in patients with autoantibody to IFN-γ.

Detailed Description
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The patients with autoantibody to IFN-γ and past or current history of proven opportunistic infection will receive 2 treatment cycles of bortezomib subcutaneously (4 injections of 1.3 mg Bortezomib /m2 body surface per cycle), followed by low dose oral cyclophosphamide for 4 month after completion treatment with bortezomib.

Official Title
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Treatment of Anti-Interferon-Gamma Autoantibody Associated Acquired Immunodeficiency Syndrome With Bortezomib: Pilot Study

Conditions
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Adult-onset Immunodeficiency

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21 - 60 years Positive anti-interferon-gamma autoantibody Anti-HIV negative Past or current infection with opportunistic infection (OI) such as nontuberculous mycobacteria, proven by culture Ability to give written consent, informed written consent Negative pregnancy test in premenopausal woman Receving antimicrobial for treatment of OI for at least one month. Exclusion Criteria: Pregnancy or lactation Absolute neutrophil count <1.5 × 109/ L or platelet count <100× 109/ L or hemoglobin level < 8 g/dL Past history of myocardial infarction or heart failure within 6 months before enrollment or prolonged QT interval > 450 msec at screening Renal insufficiency (GFR < 30 ml/min) Abnormal liver function test (AST> 3 times of UNL) Known cancer or receiving other immunosuppressive agent Known intolerability to Bortezomib

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib and cyclophosphamide<br>Two cycles of bortezomib administered subcutaneously, followed by 4 months of low dose oral cyclophosphamide. | Drug: Bortezomib<br>* Bortezomib will be subcutaneously administered in 2 treatment cycles with 4 injections of 1.3 mg Bortezomib /m2 body surface per cycle.<br>* Other names: Velcade;Drug: Cyclophosphamide<br>* Low dose cyclophosphamide will be given orally for 4 month after completion 2 cycles of bortezomib<br>* Other names: Endoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers of anti-interferon-gamma antibody after treatment with bortezomib | Change in titers of anti-interferon-gamma antibody after treatment with | 8 weeks after first dose of bortezomib (after completion 2 cycles of bortezomib) | 
| Titers of anti-interferon-gamma antibody after treatment with bortezomib and cyclophosphamide | Change in titers of anti-interferon-gamma antibody after treatment with bortezomib and cyclophosphamide | 1 year after first dose of bortezomib | 
| Adverse event | Grade 4 adverse event (probably related) | 6 months after first dose of bortezomib (after completion 4 months of cyclophosphamide) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease relapse | Worsening of symptoms and signs | 6 month and 1 year after first dose of bortezomib | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-interferon gamma autoantibody