Clinical trial NCT03103555: Treatment of Adult-Onset Immunodeficiency With Bortezomib
Official title: Treatment of Anti-Interferon-Gamma Autoantibody Associated Acquired Immunodeficiency Syndrome With Bortezomib: Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Adult-onset Immunodeficiency
Keywords: Anti-interferon gamma autoantibody
Lead sponsor: Mahidol University
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Thailand
First posted: 2017-04-06
Enrollment: 5
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Titers of anti-interferon-gamma antibody after treatment with bortezomib
timeFrame: 8 weeks after first dose of bortezomib (after completion 2 cycles of bortezomib)
measure: Titers of anti-interferon-gamma antibody after treatment with bortezomib and cyclophosphamide
timeFrame: 1 year after first dose of bortezomib
measure: Adverse event
timeFrame: 6 months after first dose of bortezomib (after completion 4 months of cyclophosphamide)
Secondary outcomes:
measure: Disease relapse
timeFrame: 6 month and 1 year after first dose of bortezomib
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital, Mahidol University
Study officials:
affiliation: Faculty of Mdicine Siriraj Hospital, Mahidol University
name: Nasikarn Angkasekwinai, MD.
role: PRINCIPAL_INVESTIGATOR
References: