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

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT02705638

Collaborator

Celgene Corporation (Industry)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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?

Condition or Disease	Intervention/Treatment	Phase
Immunoglobulin G Subclass 4 Related Disease IgG4-related Disease Autoimmune Pancreatitis IgG4-related Sclerosing Cholangitis Retroperitoneal Fibrosis	Drug: Rituximab Drug: Lenalidomide	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2016

Actual Primary Completion Date :

Apr 1, 2019

Actual Study Completion Date :

Apr 1, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Number of subjects in remission for Immunoglobulin G subclass 4 Related Disease at 24 months [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Diagnosis of active IgG4-RD based on standard pathologic or clinical criteria (see below) and requiring medical treatment
Patient is:
in relapse after prior steroid and/or rituximab (RTX) treatment or while tapering steroid treatment, OR
has disease that is refractory to steroids, OR
has contraindications to steroid therapy (including diabetes, mood disorder, obesity)
Absolute neutrophil count >1500 and platelet count >/= 100,000
Calculated creatinine clearance (or estimated GFR) greater than or equal to 60ml/min
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
Not pregnant or nursing
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
Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS™ program
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)
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)
Females must follow pregnancy testing requirements as outlined in the Revlimid REMS™ program

Exclusion criteria:

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
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
Known immunodeficiency state
New York Heart Association Classification III or IV heart disease
Active malignancy requiring therapy
Receipt of a live vaccine within 4 weeks prior to initiating study drug therapy.
Allergies: History of severe allergic reactions to human or chimeric monoclonal antibodies, murine protein, or lenalidomide
Substance abuse: Drug or alcohol abuse that could interfere with participation in the trial according to the protocol
Known anti-human anti-chimeric antibody formation
Treatment with infliximab, adalimumab, or etanercept within the past 12 months.
Currently taking azathioprine, 6-mercaptopurine, methotrexate, mycophenolate mofetil, or other conventional immunomodulators. Patients receiving these drugs must discontinue them prior to enrollment
Other investigational medication within the previous one month