Treatment of Adult-Onset Immunodeficiency With Bortezomib

Adult-onset Immunodeficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03103555
• Other study ID #: Treatment AOI with Bortezomib
• Status: Recruiting
• Phase: Phase 2
• First received: April 1, 2017
• Last updated: April 1, 2017
• Start date: February 27, 2017
• Est. completion date: November 1, 2019

Study information

• Verified date: April 2017
• Source: Mahidol University
• Contact: Nasikarn Angkasekwinai, MD.
• Phone: 6681-8708766
• Email: nasikarn[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: November 1, 2019
• Est. primary completion date: November 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Adult-onset Immunodeficiency
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Bortezomib
Bortezomib will be subcutaneously administered in 2 treatment cycles with 4 injections of 1.3 mg Bortezomib /m2 body surface per cycle.
• Cyclophosphamide
Low dose cyclophosphamide will be given orally for 4 month after completion 2 cycles of bortezomib

Locations

Country	Name	City	State
Thailand	Faculty of Medicine Siriraj Hospital, Mahidol University	Bangkok

Sponsors (2)

Lead Sponsor	Collaborator
Mahidol University	Ministry of Health, Thailand

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	Adverse event	Grade 4 adverse event (probably related)	6 months after first dose of bortezomib (after completion 4 months of cyclophosphamide)
Secondary	Disease relapse	Worsening of symptoms and signs	6 month and 1 year after first dose of bortezomib