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Treatment of Adult-Onset Immunodeficiency With Bortezomib

Primary Purpose

Adult-onset Immunodeficiency

Status

Unknown status

Phase

Phase 2

Locations

Thailand

Study Type

Interventional

Intervention

Bortezomib

Cyclophosphamide

About this trial

This is an interventional treatment trial for Adult-onset Immunodeficiency focused on measuring Anti-interferon gamma autoantibody

Eligibility Criteria

21 Years - 60 Years (Adult)All SexesDoes not accept 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

Sites / Locations

Faculty of Medicine Siriraj Hospital, Mahidol UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bortezomib and cyclophosphamide

Arm Description

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

Outcomes

Primary Outcome Measures

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

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

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

Adverse event

Grade 4 adverse event (probably related)

Secondary Outcome Measures

Disease relapse

Worsening of symptoms and signs

Full Information

NCT ID

NCT03103555

First Posted

April 1, 2017

Last Updated

April 1, 2017

Sponsor

Mahidol University

Collaborators

Ministry of Health, Thailand

1. Study Identification

Unique Protocol Identification Number

NCT03103555

Brief Title

Treatment of Adult-Onset Immunodeficiency With Bortezomib

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Unknown status

Study Start Date

February 27, 2017 (Actual)

Primary Completion Date

November 1, 2018 (Anticipated)

Study Completion Date

November 1, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mahidol University

Collaborators

Ministry of Health, Thailand

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adult-onset Immunodeficiency

Keywords

Anti-interferon gamma autoantibody

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Bortezomib and cyclophosphamide

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Other Intervention Name(s)

Velcade

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Endoxan

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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)

Title

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

Description

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

Time Frame

1 year after first dose of bortezomib

Title

Adverse event

Description

Grade 4 adverse event (probably related)

Time Frame

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

Secondary Outcome Measure Information:

Title

Disease relapse

Description

Worsening of symptoms and signs

Time Frame

6 month and 1 year after first dose of bortezomib

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Nasikarn Angkasekwinai, MD.

Phone

6681-8708766

nasikarn@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Yupin Suputtamongkol, MD.

Phone

662-4197783

ysuputtamongkol@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nasikarn Angkasekwinai, MD.

Organizational Affiliation

Faculty of Mdicine Siriraj Hospital, Mahidol University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Faculty of Medicine Siriraj Hospital, Mahidol University

City

Bangkok

ZIP/Postal Code

10700

Country

Thailand

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nasikarn Angkasekwinai, MD

Phone

66818708766

nasikarn@gmail.com

First Name & Middle Initial & Last Name & Degree

Yupin =Suputtamongkol, MD.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Treatment of Adult-Onset Immunodeficiency With Bortezomib

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