High dose immunoablation and autologous hematopoietic stem cell transplantation versus monthly intravenous pulse therapy cyclophosphamide in severe systemic sclerosis ( ‘ASTIS’-TRIAL: Autologous Stem Cell Transplantation International Scleroderma Trial) - ASTIS

• Conditions: MedDRA version: 9.1Level: LLTClassification code 10042953Term: Systemic sclerosis; Severe systemic sclerosis

• Registration Number: EUCTR2006-004598-83-GB
• Lead Sponsor: EBMT (European group for Blood and Marrow Transplantation)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10-24
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

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 < 11 g/dL, not explained by other causes than active scleroderma,
or b.
less than or equal 4 years since development of first sign of skin thickening, plus modified Rodnan skin score greater than or equal 15, plus major organ involvement (with documented evidence of onset or clinically significant worsening in the previous 6 months) as defined by either:

a) Respiratory involvement = DLCO and/or (F)VC less than or equal 80% (of predicted) and evidence of interstitial lung disease (chest X-ray and/or HR-CT scan and/or bronchoalveolar lavage and/or biopsy of the lungs) with clinically relevant obstructive disease and emphysema excluded.

b) Renal involvement = any of the following criteria: hypertension (two successive BP readings of either systolic greater than or equal 160 mm Hg or diastolic > 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

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 < 40% predicted, respiratory failure as defined by the primary endpoint

2.2 renal: creatinine clearance < 40 ml/min (measured or estimated)

2.3 cardiac: clinical evidence of refractory congestive heart failure; LVEF < 45% by multigated radionuclide angiography (MUGA) or cardiac echo; chronic atrial fibrillation necessitating oral anticoagulation; uncontrolled ventricular arrhythmia; pericardial effusion with hemodynamic consequences as evaluated by an experienced echocardiographist

2.4 liver failure as defined by a sustained 3-fold increase in serum transaminase or bilirubin

2.5 psychiatric disorders including active drug or alcohol abuse

2.6 concurrent neoplasms or myelodysplasia

2.7 bone marrow insufficiency defined as leucocytopenia < 4.0 x 109/L, thrombocytopenia < 50 x 109/L, anemia < 8 gr/dL, CD4+ T lymphopenia < 200 x 106/L

2.8 uncontrolled hypertension

2.9 uncontrolled acute or chronic infection, including HIV, HTLV-1,2 positivity

3. Previous treatments with TLI, TBI or alkylating agents including cyclophosphamide
(> 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified