Treatment of Adult-Onset Immunodeficiency With Bortezomib

Mahidol University

Status and phase: Unknown; Phase 2

Conditions: Adult-onset Immunodeficiency

Treatments: Drug: Cyclophosphamide; Drug: Bortezomib

Study type: Interventional

Funder types: Other

Identifiers

NCT03103555

Treatment AOI with Bortezomib

Details and patient eligibility

About

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.

Full 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.

Enrollment: 5 estimated patients

Sex: All

Ages: 21 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 1 patient group

Bortezomib and cyclophosphamide

Experimental group

Description:

Two cycles of bortezomib administered subcutaneously, followed by 4 months of low dose oral cyclophosphamide.

Treatment:

Drug: Bortezomib

Drug: Cyclophosphamide