Treatment of IgG4-Related Disease With Revlimid and Rituximab (TIGR2)

July 3, 2019 updated by: Thomas E. Witzig, M.D., Mayo Clinic

Treatment of IgG4-Related Disease With Revlimid and Rituximab: The TIGR2 Trial

Among persons with Immunoglobulin G subclass 4 Related Disease (IgG4)-related disease who have persistent or recurrent disease despite standard therapies, does combination therapy with rituximab and revlimid cause a sustained disease remission?

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Immunoglobulin G subclass 4 Related Disease (IgG4-RD) is a recently recognized systemic fibroinflammatory condition. Various manifestations of IgG4-RD were previously recognized in individual organ systems, but these entities (including autoimmune pancreatitis, orbital pseudotumor, Reidel's thyroiditis, retroperitoneal fibrosis, idiopathic sialadenitis and dacryoadenitis, etc) are now recognized as manifestations of a common disease process that can affect any organ system. IgG4-RD is characterized by distinctive histologic findings of tissue infiltration by IgG4-positive plasma cells together with storiform fibrosis and obliterative phlebitis. Both clinical and pathologic consensus diagnostic criteria have been defined. Serum IgG4 concentration is a biomarker for IgG4-RD and is elevated in 70% to 90% of patients with active disease.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. Diagnosis of active IgG4-RD based on standard pathologic or clinical criteria (see below) and requiring medical treatment

  2. Patient is:

    1. in relapse after prior steroid and/or rituximab (RTX) treatment or while tapering steroid treatment, OR
    2. has disease that is refractory to steroids, OR
    3. has contraindications to steroid therapy (including diabetes, mood disorder, obesity)
  3. Absolute neutrophil count >1500 and platelet count >/= 100,000
  4. Calculated creatinine clearance (or estimated GFR) greater than or equal to 60ml/min
  5. In patients without hepatobiliary involvement by IgG4-RD, total bilirubin less than or equal to 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) less than or equal to 3 x ULN
  6. Not pregnant or nursing
  7. All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS™) program, and be willing and able to comply with the requirements of the REMS™ program
  8. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS™ program
  9. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight heparin)
  10. Agrees to use acceptable methods of birth control during and for 12 months after completion of study drug therapy (applies to all men, and women of child bearing potential)
  11. Females must follow pregnancy testing requirements as outlined in the Revlimid REMS™ program

Exclusion criteria:

  1. Predominant changes of fibrosis (as opposed to active cellular inflammation) within the organs affected by IgG4-RD, such that the likelihood of a disease response to treatment is low
  2. Presence of active infection that would interfere with therapy on this study, including positive serum hepatitis B surface antigen, HIV or active hepatitis C virus (HCV) infection, untreated syphilis or tuberculosis, clinical history of multiple herpes virus reactivations
  3. Known immunodeficiency state
  4. New York Heart Association Classification III or IV heart disease
  5. Active malignancy requiring therapy
  6. Receipt of a live vaccine within 4 weeks prior to initiating study drug therapy.
  7. Allergies: History of severe allergic reactions to human or chimeric monoclonal antibodies, murine protein, or lenalidomide
  8. Substance abuse: Drug or alcohol abuse that could interfere with participation in the trial according to the protocol
  9. Known anti-human anti-chimeric antibody formation
  10. Treatment with infliximab, adalimumab, or etanercept within the past 12 months.
  11. Currently taking azathioprine, 6-mercaptopurine, methotrexate, mycophenolate mofetil, or other conventional immunomodulators. Patients receiving these drugs must discontinue them prior to enrollment
  12. Other investigational medication within the previous one month

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab and Lenalidomide
All subjects will receive Rituxan 1,000 mg intravenously on days 1 and 15, as well as Revlimid 20 mg orally per day on days 1-21, 29-49, and 57-77.
Drug: Rituximab
All subjects will receive Rituxan 1,000 mg intravenously on days 1 and 15.
Other Names:
  • Rituxan
Drug: Lenalidomide
All subjects will receive Revlimid 20 mg orally per day on days 1-21, 29-49, and 57-77.
Other Names:
  • Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of subjects in remission for Immunoglobulin G subclass 4 Related Disease at 24 months
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

Celgene Corporation

Investigators

  • Principal Investigator: Mark D Topazian, MD, Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2016

Primary Completion (Actual)

April 1, 2019

Study Completion (Actual)

April 1, 2019

Study Registration Dates

First Submitted

March 7, 2016

First Submitted That Met QC Criteria

March 7, 2016

First Posted (Estimate)

March 10, 2016

Study Record Updates

Last Update Posted (Actual)

July 8, 2019

Last Update Submitted That Met QC Criteria

July 3, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-003700

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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