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A MultiCenter Study of Combined PEX, Rituximab, and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations

Primary Purpose

Idiopathic Pulmonary Fibrosis

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Standard Steroid Treatment

The Standard Steroid Treatment, Plasma Exchange and rituximab

About this trial

This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis focused on measuring Acute Idiopathic Pulmonary Fibrosis Exacerbations, Idiopathic Pulmonary Fibrosis, IPF

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:

A diagnosis of idiopathic pulmonary fibrosis that fulfills American Thoracic Society Consensus Criteria.1
Unexplained worsening or development of dyspnea or hypoxemia within the preceding 30 days.
Radiographic imaging showing ground-glass abnormality and/or consolidation superimposed on a reticular or honeycomb pattern consistent with UIP.

EXCLUSION CRITERIA

Diagnosis of documented infection, thromboembolic disease, an additional etiology for acute lung injury/adult respiratory distress syndrome, congestive heart failure.
Presence of active hepatitis B infection.
Coagulopathy defined as an INR > 1.8, PTT > 2 x control, and platelet count < 50K.
Hyperosmolar state or diabetic ketoacidosis to suggest uncontrolled diabetes mellitus or uncontrolled hypertension.
Hemodynamic instability.
History of reaction to blood products, murine-derived products, or prior exposures to human-murine chimeric antibodies,
History of malignancy.
Unwillingness to accept a blood transfusion.
Unwillingness to agree to full supportive medical care (e.g., intubation) for up to 2 weeks after enrollment.
Inability or unwillingness to complete post-treatment surveillance for 60 days.
Diagnosis of major comorbidities expected to interfere with subjects study participation for 28 days.
Treatment for >5 days within the preceding month with >20 mg prednisone (or equivalent dose corticosteroid) or any treatment during the preceding month with a potent cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, mycophenolate, azathiaprine, calcineurin inhibitors, etc.) unless the patient has a BAL negative for opportunistic pathogens (e.g, Pneumocystis, viruses, intracellular organisms, mycobacteria, etc.).
Current treatment with an angiotensin converting enzyme inhibitor that cannot be discontinued and/or substituted with another antihypertensive agent (to minimize potential hemodynamic complications during PEX).

Sites / Locations

Geisinger Medical Center
Temple University Medical Center
University of Pittsburgh
University of Texas Medical Branch - Galveston
Inova Fairfax Heart and Vascular Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm A - Standard Steroid Treatment

Arm B - Experimental Treatment

Arm Description

Outcomes

Primary Outcome Measures

Reduction of autoantibody titers

The primary end-point is reduction of autoantibody titers to cultured human primary pulmonary cells, comparing baseline measures of each individual to results of their measures on day 28, or the latest measure among patients who do not survive to day 28.

Secondary Outcome Measures

IgG concentrations

Treatment-related effects on plasma IgG concentrations

B-cell counts

Adverse event (AE) rates

Full Information

NCT ID

NCT01524068

First Posted

January 27, 2012

Last Updated

January 4, 2016

Sponsor

University of Pittsburgh

1. Study Identification

Unique Protocol Identification Number

NCT01524068

Brief Title

A MultiCenter Study of Combined PEX, Rituximab, and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations

Official Title

A Multicenter, Open-Label, Phase II Study of Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids in Patients With Acute Idiopathic Pulmonary Fibrosis Exacerbations

Study Type

Interventional

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Withdrawn

Study Start Date

September 2012 (undefined)

Primary Completion Date

June 2016 (Anticipated)

Study Completion Date

June 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pittsburgh

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a randomized, multi-center, open-label Phase II clinical trial to determine the efficacy of combined plasma exchange (PEX), rituximab, and conventional corticosteroid administration, in comparison to corticosteroids alone, among patients with acute Idiopathic Pulmonary Fibrosis (IPF) exacerbations. The investigators central hypothesis is that antibody-mediated autoimmunity can play an important role in IPF exacerbations. The investigators propose to test our central hypothesis by establishing the efficacy of autoantibody removal by plasma exchange (PEX), in conjunction with B-cell depletion by rituximab to deplete immunoglobulins and minimize their further production, among patients with acute IPF exacerbations. The primary goal of this randomized, multi-center, open-label Phase II clinical trial is to determine effects of combined plasma exchange (PEX), rituximab, and conventional corticosteroid administration on selected, relevant immunological parameters, in comparison to effects of steroids alone, among AE-IPF patients. The investigators anticipate the findings of this will lead to larger incremental trial(s) to determine actual clinical efficacy of this treatment. A total of 40 subjects will be enrolled in this multi-center trial from 5 participating medical centers.

Detailed Description

6. Conditions and Keywords

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

Idiopathic Pulmonary Fibrosis

Keywords

Acute Idiopathic Pulmonary Fibrosis Exacerbations, Idiopathic Pulmonary Fibrosis, IPF

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A - Standard Steroid Treatment

Arm Type

Experimental

Arm Title

Arm B - Experimental Treatment

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Standard Steroid Treatment

Intervention Description

One gm of methylprednisolone i.v., on day 0, followed by 40 mg/day i.v. on days 1-4, and days 6-12 (or the p.o. prednisone equivalent). Methylprednisolone 100 mg i.v. will be administered on days 5 and 13. Steroid doses will then be 20 mg methylprednisolone i.v. (or p.o. prednisone equivalent) from days 14-28, and then reduced thereafter at the discretion of the PI at each site.

Intervention Type

Drug

Intervention Name(s)

The Standard Steroid Treatment, Plasma Exchange and rituximab

Intervention Description

The Standard Steroid Treatment and, after insertion of a dialysis/apheresis catheter into a central vein, followed by initiation of the PEX and rituximab regimens.

Primary Outcome Measure Information:

Title

Reduction of autoantibody titers

Description

Time Frame

Baseline to Day 28

Secondary Outcome Measure Information:

Title

IgG concentrations

Description

Treatment-related effects on plasma IgG concentrations

Time Frame

Baseline to Day 60

Title

B-cell counts

Time Frame

Baseline to Day 60

Title

Adverse event (AE) rates

Time Frame

Baseline to Day 60

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA: A diagnosis of idiopathic pulmonary fibrosis that fulfills American Thoracic Society Consensus Criteria.1 Unexplained worsening or development of dyspnea or hypoxemia within the preceding 30 days. Radiographic imaging showing ground-glass abnormality and/or consolidation superimposed on a reticular or honeycomb pattern consistent with UIP. EXCLUSION CRITERIA Diagnosis of documented infection, thromboembolic disease, an additional etiology for acute lung injury/adult respiratory distress syndrome, congestive heart failure. Presence of active hepatitis B infection. Coagulopathy defined as an INR > 1.8, PTT > 2 x control, and platelet count < 50K. Hyperosmolar state or diabetic ketoacidosis to suggest uncontrolled diabetes mellitus or uncontrolled hypertension. Hemodynamic instability. History of reaction to blood products, murine-derived products, or prior exposures to human-murine chimeric antibodies, History of malignancy. Unwillingness to accept a blood transfusion. Unwillingness to agree to full supportive medical care (e.g., intubation) for up to 2 weeks after enrollment. Inability or unwillingness to complete post-treatment surveillance for 60 days. Diagnosis of major comorbidities expected to interfere with subjects study participation for 28 days. Treatment for >5 days within the preceding month with >20 mg prednisone (or equivalent dose corticosteroid) or any treatment during the preceding month with a potent cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, mycophenolate, azathiaprine, calcineurin inhibitors, etc.) unless the patient has a BAL negative for opportunistic pathogens (e.g, Pneumocystis, viruses, intracellular organisms, mycobacteria, etc.). Current treatment with an angiotensin converting enzyme inhibitor that cannot be discontinued and/or substituted with another antihypertensive agent (to minimize potential hemodynamic complications during PEX).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven Duncan, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

Geisinger Medical Center

City

Danville

State/Province

Pennsylvania

ZIP/Postal Code

17822

Country

United States

Facility Name

Temple University Medical Center

City

Philladelphia

State/Province

Pennsylvania

ZIP/Postal Code

19140

Country

United States

Facility Name

University of Pittsburgh

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

University of Texas Medical Branch - Galveston

City

Galveston

State/Province

Texas

ZIP/Postal Code

77555

Country

United States

Facility Name

Inova Fairfax Heart and Vascular Institute

City

Falls Church

State/Province

Virginia

ZIP/Postal Code

22042

Country

United States

12. IPD Sharing Statement

Learn more about this trial

A MultiCenter Study of Combined PEX, Rituximab, and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations

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