Treatment of Adult-Onset Immunodeficiency With Bortezomib

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

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.

Study Overview

• Status: Unknown
• Conditions: Adult-onset Immunodeficiency
• Intervention / Treatment: Drug: Bortezomib; Drug: Cyclophosphamide

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 Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Faculty of Medicine Siriraj Hospital, Mahidol University
    • Contact: Nasikarn Angkasekwinai, MD; Phone Number: 66818708766; Email: nasikarn@gmail.com
    • Sub-Investigator: Yupin =Suputtamongkol, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bortezomib and cyclophosphamide; Two cycles of bortezomib administered subcutaneously, followed by 4 months of low dose oral cyclophosphamide.	Drug: Bortezomib; Bortezomib will be subcutaneously administered in 2 treatment cycles with 4 injections of 1.3 mg Bortezomib /m2 body surface per cycle.; Other Names: Velcade; Drug: Cyclophosphamide; Low dose cyclophosphamide will be given orally for 4 month after completion 2 cycles of bortezomib; Other Names: Endoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
Adverse event	Grade 4 adverse event (probably related)	6 months after first dose of bortezomib (after completion 4 months of cyclophosphamide)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease relapse	Worsening of symptoms and signs	6 month and 1 year after first dose of bortezomib

Collaborators and Investigators

• Sponsor: Mahidol University
• Collaborators: Ministry of Health, Thailand
• Investigators: Principal Investigator: Nasikarn Angkasekwinai, MD., Faculty of Mdicine Siriraj Hospital, Mahidol University

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2017
• Primary Completion (Anticipated): November 1, 2018
• Study Completion (Anticipated): November 1, 2019

Study Registration Dates

• First Submitted: April 1, 2017
• First Submitted That Met QC Criteria: April 1, 2017
• First Posted (Actual): April 6, 2017

Study Record Updates

• Last Update Posted (Actual): April 6, 2017
• Last Update Submitted That Met QC Criteria: April 1, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Anti-interferon gamma autoantibody
• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Bortezomib
• Other Study ID Numbers: Treatment AOI with Bortezomib

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No