A Protocol Based Treatment for Debilitating Fibrosing Skin Disorders With (Anti-CD 20), Rituximab, Evaluating Safety and Efficacy

Inclusion criteria

• (Fe) male >, = 18 years
• Fibrosing skin disorder, not fulfilling the ACR criteria for diffuse SSc
• Inadequate response to methotrexate (at least 12 weeks 10 mg/w, except if not tolerated or contra-indicated
• Debilitating disease defined by either one of the following:
• Restriction of mobility
• Disfiguration: eg: facial involvement
• Severe Internal Organ involvement
• Contraception for women with childbearing potential. Sexual abstinence is an alternative to contraception.

Exclusion criteria

• FVC<, = 50%
• LVEF<, = 40% of predicted value,
• DLCO<, = 40% of predicted value
• Exclusion criteria as specifically described in the protocol for anti-CD-20:
• Lack of peripheral venous access.
• Pregnancy or breast feeding.
• Significant cardiac or pulmonary disease (including obstructive pulmonary disease).
• Evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine or gastrointestinal disorders which, in the investigator's opinion, would preclude patient participation.
• Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.
• Known active infection of any kind (excluding fungal infections of mail beds), or any major episode of infection requiring hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or completion of oral anti-infectives within 2 weeks prior to baseline.
• History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks prior to baseline.
• History of serious recurrent or chronic infection (for screening for a chest infection a chest radiograph will be performed at screening if not performed within 12 weeks prior to screening).
• History of cancer, including solid tumors, hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured).
• History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of rituximab or to murine proteins.
• Concurrent treatment with any biologic agent or DMARD other than MTX. Treatment must be discontinued 14 days prior to baseline , except for the following: azathioprine for ≥ 28 days; leflunomide for ≥ 8 weeks (or ≥ 14 days after 11 days of standard cholestyramine or activated charcoal washout); infliximab ≥ 8 weeks; adalimumab ≥ weeks.
• Previous treatment with > 1 biological agent.
• Treatment with any investigational agent within 28 days of baseline or 5 half-lives of the investigational drug (which ever is the longer).
• Receipt of any vaccine within 28 days prior to baseline
• Intolerance or contraindications to i.v. glucocorticoids.
• Positive serum human chorionic gonadotropin (hCG) measured at screening or a positive pregnancy test prior to the first rituximab infusion.
• Positive tests for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology.
• Hemoglobin < 8.0 g/dL.
• Concentrations of serum IgG and/or IgM below 5.0 and 0.40 mg/mL, respectively.
• Absolute neutrophil count (ANC) < 1.5 X 10³/µL.