Ruxolitinib in Previously Treated Idiopathic Multicentric Castleman Disease

Inclusion Criteria: 1. Male or female, age 18-80 2. Documented disease history consistent with diagnostic criteria for iMCD • Indication of clinico-histopathological features consistent with iMCD as determined by a licensed pathologist in a diagnostic pathology report, or a CAS grade of at least 3 in the companion registry study (ACCELERATE). 3. Refractory (patient did not achieve sufficient disease control with anti-IL-6 therapy, as determined by the site investigator), relapsed (return of symptoms while on therapy), or inability to tolerate anti-IL-6 or anti-IL-6 receptor therapy 4. Evidence of active disease, defined by at least two of: constitutional symptoms (fatigue, night sweats, fever, weight change), hemoglobin \< lower limit of normal, C-reactive protein \> upper limit of normal (or \>10 mg/L), or albumin \< lower limit of normal (\<3.5 g/dL), at lease one lymph node meeting modified Cheson criteria 5. Ability to consume oral medication in the form of a tablet 6. Ability to provide informed consent prior to any study-specific activities Exclusion Criteria: 1. Subjects cannot be pregnant or nursing females • Women of childbearing potential must have a negative pregnancy test documented at the Baseline Visit. Subjects of reproductive potential may not participate unless they have agreed, as part of the informed consent, to use an effective contraceptive method for the duration of the study and for at least 12 weeks after ending treatment 2. Subjects cannot have received any systemic therapy(ies) intended to treat iMCD other than corticosteroids or anti-IL-6 therapy within 14 days of enrollment • Corticosteroid treatment must have been initiated more than 28 days prior to enrollment and be maintained at a stable or tapering dose (prednisone or equivalent up to 1 mg/kg/day) prior to enrollment; dose cannot be elevated for the duration of the study but can be maintained or tapered • For subjects who cannot or are unwilling to undergo a 14-day washout period from their anti-IL-6 therapy: i. Anti-IL-6 therapy may be permitted if the subject has been on therapy for at least 3 months, no toxicity has been documented, and sufficient disease control is not achieved ii. Anti-IL-6 therapy is recommended to be discontinued within the first 6 weeks after starting ruxolitinib 3. Subjects cannot have previously received ruxolitinib monotherapy or combination therapy to treat iMCD 4. Subjects cannot have uncontrolled infection or infectious disease(s) that is/are exclusionary for / mimickers of iMCD * Fungal disease must be stable for at least two weeks before enrollment * Subjects with history of recent bacteremia must have a documented negative blood culture before enrollment * Subjects with past history of non-therapy related opportunistic infection should discuss eligibility and possible immunologic evaluation with the licensed site investigator prior to enrollment 5. Subjects cannot have: * ECOG \>3 * eGFR \<30mL/min/1.73 m2 or creatinine \>3.0 mg/dL * Absolute neutrophil count (ANC) \< 1000 x 109/L * Hemoglobin ≤ 6.5 g/dL (transfusion independent, defined as not receiving a red blood cell transfusion for ≥ 7 days prior) * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) laboratory values greater than three times the upper limit of normal * Albumin \< 2 g/dL (transfusion independent, defined as not receiving intravenous albumin for ≥ 7 days prior) * Platelet count ≤ 40 x 109/L (transfusion independent, defined as not receiving platelet transfusion for ≥ 7 days prior) * Pulmonary involvement or interstitial pneumonitis with dyspnea (adequate pulmonary function is defined as pulse oximetry \> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest, history of interstitial pneumonitis, etc.) * Fasting cholesterol \> 300 mg/dL or fasting triglyceride \> 400 mg/dL 6. Subjects cannot have rheumatologic disease(s) that is/are exclusionary for / mimickers of iMCD 7. Subjects cannot have a prior malignancy except for: (1) adequately treated basal cell or squamous cell skin cancer, (2) in situ cervical cancer, or (3) other cancer for which the subject has not received treatment within one year prior to enrollment • Other cancers will only be acceptable if the patient's life expectancy exceeds five years and they are not exclusionary diagnoses for iMCD 8. Subjects cannot have a documented history of human immunodeficiency virus (HIV) or HHV-8 infection, or severe combined immunodeficiency syndrome 9. Subjects cannot have active infections of mycobacterium tuberculosis, hepatitis B, or hepatitis C due to the potential reactivation with ruxolitinib * A positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antigen (HBsAb) positive and hepatitis B core antibody (HBcAb) negative), or a fully resolved acute hepatitis B infection is not an exclusion criterion. * Subjects with an indolent chronic hepatitis B infection (normal ALT, AST, albumin and no radiographic or biopsy evidence of cirrhosis) may be eligible. * Subjects with active hepatitis C are excluded. Subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). 10. Subjects cannot have had any major adverse cardiac events, including ischemic stroke and myocardial infarction, within 6 months of enrollment 11. Subjects cannot have ongoing or planned participation in another clinical trial involving iMCD directed treatment or that involves immunomodulatory or anti-neoplastic treatment 12. Subjects cannot have prior sensitivity / allergy to any formulation of ruxolitinib, its components, or its analogues 13. Subjects cannot have serious medical illness, or psychiatric illness or disorders that could potentially interfere with the completion of treatment according to this protocol or participation in the trial 14. Subjects cannot have psychiatric disorders that compromise their ability to provide informed consent 15. Subjects cannot have any other condition or finding that, in the opinion of the investigator, would make participation in this trial inappropriate