Treatment of Adult-Onset Immunodeficiency With Bortezomib

Phase 2

• Conditions: Adult-onset Immunodeficiency
• Interventions: Drug: Bortezomib; Drug: Cyclophosphamide

• Registration Number: NCT03103555
• Lead Sponsor: Mahidol University

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.

Study Timeline

• Study Start: 2017-02-27
• Status Verified: 2017-04
• Study First Submitted: 2017-04-01
• Study First Submitted QC: 2017-04-01
• Last Update Submitted: 2017-04-01
• Study First Posted: 2017-04-06
• Last Update Posted: 2017-04-06
• Primary Completion: 2018-11-01
• Study Completion: 2019-11-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bortezomib and cyclophosphamide	Bortezomib	Two cycles of bortezomib administered subcutaneously, followed by 4 months of low dose oral cyclophosphamide.
Bortezomib and cyclophosphamide	Cyclophosphamide	Two cycles of bortezomib administered subcutaneously, followed by 4 months of low dose oral cyclophosphamide.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Disease relapse	6 month and 1 year after first dose of bortezomib	Worsening of symptoms and signs

Trial Locations

Locations (1)

Faculty of Medicine Siriraj Hospital, Mahidol University; 🇹🇭 Bangkok, Thailand