To evaluate the safety and efficacy of anti-CD20 therapy with respect to: - Clinical and laboratory adverse events, as measured every three months. - Survival and prevention of major organ failure (referred to as ¡¥event-free survival¡¦ which is considered the primary endpoint). - Impact on skin thickening, visceral involvement, functional status, and quality of life
Conditions
Interventions
This investigation is a placebo-controlled randomized double blinded single-center phase II study, administering intravaneously monoclonal anti-CD20 antibody or placebo together with a corticosteroid
Sponsors
ROCHE
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age between 18 and 70 years. 2. Established diagnosis of systemic sclerosis according to ARA-criteria (appendix). 3. Informed consent.
Exclusion criteria
Exclusion criteria: 1. Pregnancy or unwillingness to use adequate contraception during study. 2. Previous treatments with biological agents, cell depleting therapies including investigational agents. 3. Significant exposure to bleomycin, tainted rapeseed oil, vinyl chloride, trichlorethylene or silica; eosinophilic myalgia syndrome; eosinophilic fasciitis. 4. History of allergic or anaphylactic reaction to a biological agent or known hypersensitivity to any component of anti-CD20 monoclonal antibodies or to murine proteins. 5. History of deep tissue infection (e.g. Fasciitis, abscess, osteomyelitis) within 1 year prior to baseline. 6. History of serious chronic or recurrent infection within 12 weeks prior to baseline, including HIV, HTLV-1,2 positivity. 7. History of cancer, including solid tumors, hematological malignancies and carcinoma in situ (except for basal cell and squamous cell carcinoma of the skin that have been treated and cured). 8. Concurrent liver failure as defined by a sustained 3-fold increase in serum transaminase or bilirubin. 9. Active drug or alcohol abuse or persistent psychiatric disorders that prevent inclusion. 10. Uncontrolled hypertension. 11. Poor compliance of the patient as assessed by the referring physicians. 12. Receipt of any vaccine 28 days prior to baseline. 13. Intolerance or contraindications to IV glucocorticoids. 14. Positive tests for HbsAg, Hepatitis core antibody or hepatitis C serology. 15. Concentrations of serum IgG and /or IgM below 5.0 and 0.40 mg/ mL. 16. Absolute neutrophil count of less than 1.0x 109/L.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Treatment related mortality is defined as any death during the study period that cannot be attributed to progression of the disease according to the consensus opinion. 2. Treatment toxicity will be assessed using WHO toxicity parameters (expressed as maximum grade toxicity per organ system) (Appendix) in consecutive 3-month periods following randomization. 3. Efficacy will be assessed as progression-free survival, defined as the time in days since the day of randomization until any of the following changes from baseline has been documented at two consecutive 3-month evaluations: -death -„d 10% drop in (F)VC and/or „d 15% drop in DLCO (of predicted values) -„d 15% drop in LVEF by MUGA -„d 15% drop in body weight -„d 30% drop in creatinine clearance -„d 30% increase in Modified Rodnan skin score -„d 0.5 increase in SHAQ Changes during the study period (from baseline until completion of 2 years follow-up) in the following parameters : -Modified Rodnan Skin score -(F)VC and DLCO -LVEF -Weight (Kg) -SF-36 -EuroQol (EQ-5D) -gas (pO2, pCO2, p(A-a)O2) at room air | — |
Secondary
| Measure | Time frame |
|---|---|
| - To evaluate whether disease activity correlates with immunological parameters, including immunopathology of skin, immune reconstitution, and autoantibodies. - To search for predictive factors (clinical and immunological) of response. | — |
Contacts
Public ContactA.J.M. Schuerwegh
Leiden University Medical Center (LUMC)
Outcome results
None listed