Treatment of Adult-Onset Immunodeficiency With Bortezomib

Mahidol University5 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Adult-onset Immunodeficiency

Interventions

BortezomibDRUG

Bortezomib will be subcutaneously administered in 2 treatment cycles with 4 injections of 1.3 mg Bortezomib /m2 body surface per cycle.

CyclophosphamideDRUG

Low dose cyclophosphamide will be given orally for 4 month after completion 2 cycles of bortezomib

Eligibility

Sex: ALLMin age: 21 YearsMax age: 60 Years

Medical Language ↔ Plain English

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

Locations (1)

Faculty of Medicine Siriraj Hospital, Mahidol University

Bangkok, Bangkok, Thailand

RECRUITING

Outcomes

Primary Outcomes

Titers of anti-interferon-gamma antibody after treatment with bortezomib

Change in titers of anti-interferon-gamma antibody after treatment with

Time frame: 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

Time frame: 1 year after first dose of bortezomib

Adverse event

Grade 4 adverse event (probably related)

Time frame: 6 months after first dose of bortezomib (after completion 4 months of cyclophosphamide)

Secondary Outcomes

Disease relapse

Worsening of symptoms and signs

Time frame: 6 month and 1 year after first dose of bortezomib

Central Contacts

Nasikarn Angkasekwinai, MD.

CONTACT

6681-8708766 nasikarn@gmail.com

Yupin Suputtamongkol, MD.

CONTACT

662-4197783 ysuputtamongkol@gmail.com

Data from ClinicalTrials.gov

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