Treatment of IgG4-Related Disease With Revlimid and Rituximab

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