pfront autologous hematopoietic stem cell transplantation versus immunosuppressive medication in early diffuse cutaneous systemic sclerosis: an international multicentre, open-label, randomized con-trolled trial
- Conditions
- Systemic Sclerosis
- Registration Number
- NL-OMON26075
- Lead Sponsor
- niversity Medical Centre Utrecht
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 120
1. Age between 18 and 65 years.
2. Fulfilling the 2013 ACR-EULAR classification criteria for SSc (appendix B).
3. Disease duration = 2 years (from onset of first non-Raynaud’s symptoms) and diffuse cutaneous disease with
- mRSS = 15 and/or
- clinically significant organ involvement as defined by either:
a)respiratory involvement =
i. DLCO and/or (F)VC = 85% (of predicted) and evidence of interstitial lung disease on HR-CT scan with clinically relevant obstructive disease and emphysema excluded.
ii. Patients with a DCLO and/or FVC > 85%, but with a progressive course of lung disease: defined as relative decline of >10% in FVC predicted and/or TLC predicted, or >15% in DLCO predicted and evidence of interstitial lung disease on HR-CT scan with clinically relevant obstructive disease and emphysema excluded, within 12 months. Intercurrent infections excluded.
b)renal involvement = any of the following criteria: hypertension (two successive BP readings
of either systolic = 160 mm Hg or diastolic > 110 mm Hg, at least 12 hours apart), persistent
urinalysis abnormalities (proteinuria, haematuria, casts), microangiopathic haemolytic anaemia,
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 atrial fibrillation or flutter, atrial paroxysmal tachycardia or ventricular tachycardia, 2nd or 3rd degree AV block, pericardial effusion (not leading to hemodynamic problems), myocardi-tis; non-scleroderma related causes must have been reasonably excluded.
4. Written Informed consent
A potential subject who meets any of the following criteria will be excluded from participation in this study:
1. Pregnancy or unwillingness to use adequate contraception during study
2. Concomitant severe disease =
a)respiratory: resting mean pulmonary artery pressure (mPAP) > 20 mmHg (by right heart catheterisa
tion), DLCO < 40% predicted, respiratory failure as defined by the primary endpoint
b)renal: creatinine clearance < 40 ml/min (measured or estimated)
c)cardiac: clinical evidence of refractory congestive heart failure; LVEF < 45% by cardiac echo or cardiac
MR; chronic atrial fibrillation necessitating oral anticoagulation; uncontrolled ventricular
arrhythmia; pericardial effusion with hemodynamic consequences
d)liver failure as defined by a sustained 3-fold increase in serum transaminase or bilirubin, or a Child-
Pugh score C
e)psychiatric disorders including active drug or alcohol abuse
f)concurrent neoplasms or myelodysplasia
g)bone marrow insufficiency defined as leukocytopenia < 4.0 x 109/L, thrombocytopenia < 50
x 109/L, anaemia < 8 gr/dL, CD4+ T lymphopenia < 200 x 106/L
h)uncontrolled hypertension
i)uncontrolled acute or chronic infection, including HIV, HTLV-1,2 positivity
j)ZUBROD-ECOG-WHO Performance Status Scale > 2
3. Previous treatments with immunosuppressants > 6 months including MMF, methotrexate, azathioprine, rituximab, tocilizumab, glucocorticosteroids.
4. Previous treatments with TLI, TBI or alkylating agents including CYC.
5. Significant exposure to bleomycin, tainted rapeseed oil, vinyl chloride, trichlorethylene or silica;
6. eosinophilic myalgia syndrome; eosinophilic fasciitis.
7. Poor compliance of the patient as assessed by the referring physicians.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary endpoint is event-free survival. Event-free survival is defined as the time in days from<br>the day of randomisation until the occurrence of death due to any cause or the development of<br>persistent major organ failure (heart, lung, kidney) defined as follows:<br>•Heart: left ventricular ejection fraction < 30% by cardiac MR (or cardiac echo)<br>•Lungs: respiratory failure = resting arterial oxygen tension (PaO2) < 8 kPa (< 60 mmHg) and/or resting arterial carbon dioxide tension (PaCO2) > 6.7 kPa (> 50 mmHg) without oxygen supply<br>•Kidney: need for renal replacement therapy<br><br>Note 1. When major organ failure has occurred, its persistence is to be confirmed by<br>repeated evaluation after 3 months.<br><br>Note 2. Cardiac MR is considered the gold standard for assessment of LVEF.<br>LVEF measurements by cardiac echo (instead of cardiac MR) will be accepted when baseline and follow-up eval-uations have been performed by the same experienced echocardiologist.<br>
- Secondary Outcome Measures
Name Time Method