Severe systemic sclerosis MedDRA version: 9.1 Level: LLT Classification code 10042953 Term: Systemic sclerosis
Conditions
Interventions
Trade Name: Cyclophosphamide
Product Name: Cyclophosphamide
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50180
Current Sponsor code: Cyclophosphamide
Con
Sponsors
EBMT (European group for Blood and Marrow Transplantation)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age between 18 and 65 years. 2. Established diagnosis of systemic sclerosis according to ARA-criteria. 3. Diffuse scleroderma with disease duration either: a. less than or equal 2 years since development of first sign of skin thickening, plus modified Rodnan skin score greater than or equal 20, plus involvement of trunk plus ESR > 25 mm/1st hour and/or Hb 110 mm Hg, at least 12 hours apart), persistent urinalysis abnormalities (proteinuria, hematuria, casts), microangiopathic hemolytic anemia, new renal insufficiency (serum creatinine > upper limit of normal); non-scleroderma related causes (e.g. medication, infection etc.) must be reasonably excluded. c) Cardiac involvement = any of the following criteria: reversible congestive heart failure, atrial or ventricular rhythm disturbances such as recurrent episodes of atrial fibrillation or flutter, recurrent atrial paroxysmal tachycardia or ventricular tachycardia, 2nd or 3rd degree AV-block, pericardial effusion; non-scleroderma related causes must have been reasonably excluded by an experienced cardiologist. 4. Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnancy or unwillingness to use adequate contraception during study 2. Concomitant severe disease = 2.1 respiratory: mean PAP > 50 mmHg (by cardiac echo or right heart catheterization), DLCO 5 g i.v. cumulative, or > 3 months oral up to 2 mg/kg b.wt). 4. Significant exposure to bleomycin, tainted rapeseed oil, vinyl chloride, trichlorethylene or silica; eosinophilic myalgia syndrome; eosinophilic fasciitis. 5. Poor compliance of the patient as assessed by the referring physicians.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the potential clinical benefit of high dose immunoablation and autologous stem cell transplantation in comparison to intravenous pulse therapy cyclophosphamide, with respect to: - Survival and prevention of major organ failure (‘event-free survival’) - Safety - Impact on skin thickening, visceral involvement, functional status, and quality of life ;Secondary Objective: 1. To evaluate (in both treatment arms) whether disease activity correlates with immunological parameters, including immunopathology of skin, immune reconstitution, and autoantibodies. 2. To search for predictive factors (clinical and immunological) of response. ;Primary end point(s): The primary endpoint is event-free survival. Event-free survival is defined as the time in days from the day of randomization until the occurrence of death due to any cause or the development of persistent1 major organ failure (heart, lung, kidney) defined as follows: • Heart: left ventricular ejection fraction 6.7 kPa (> 50 mmHg) without oxygen supply • Kidney: need for renal replacement therapy | — |
Countries
United Kingdom
Outcome results
None listed