pfront autologous hematopoietic stem cell transplantation versus immunosuppressive medication in early diffuse cutaneous systemic sclerosis: an international multicentre, open-label, randomized controlled trial
- Conditions
- diffuse cutaneous systemic sclerosisscleroderma10010761
- Registration Number
- NL-OMON52909
- Lead Sponsor
- niversitair Medisch Centrum Utrecht
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 60
1. Age between 18 and 65 years.
2. Fulfilling the 2013 ACR-EULAR classification criteria
3. Disease duration <= 2 years (from onset of first non-Raynaud*s symptoms) and
- mRSS >= 15 (diffuse skin pattern) and/or
- clinically significant organ involvement as defined by either:
a) respiratory involvement
b) renal involvement
c) cardiac involvement
1. Pregnancy or unwillingness to use adequate contraception during study
2. Concomitant severe disease =
a) respiratory:
- pulmonary hypertension: a resting mean pulmonary artery pressure (mPAP) >
25 mmHg (by right heart catheterisation),
- DLCO < 40% predicted or
- respiratory failure as defined by the primary endpoint (see 7.1)
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 (10)
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, leading to exclusion of cyclo-
phosphamide, mycophenolate mofetil or autologous stem cell transplantation in
routine clinical practice.
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 (systolic blood pressure >150mmHg despite
medication)
Blood pressure needs to be controlled prior to inclusion
i) uncontrolled acute or chronic infection, including HIV, HTLV-1,2 positivity,
leading to exclusion of cyclo-
phosphamide, mycophenolate mofetil or autologous stem cell transplantation in
routine clinical practice.
Infection needs to be treated/controlled prior to inclusion.
j) ZUBROD-ECOG-WHO Performance Status Scale > 2
k) Known hypersensitivity to any of the study drug constituents
3. Previous treatments with immunosuppressants > 6 months including MMF,
methotrexate, azathioprine, rituxi-mab, tocilizumab, glucocorticosteroids.
4. Previous treatments with TLI, TBI or alkylating agents including
cyclophosphamide.
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 <p>The main study parameter is event-free survival after randomisation/treatment<br /><br>start. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary efficacy endpoints: Overall Survival (OS), progression-free survival,<br /><br>number of participants that need rescue therapy (i.e. the alternative<br /><br>treatment) due to treatment failure. Treatment related mortality, treatment<br /><br>toxicity, and changes in mRSS, FVC, TLC and DLCO, nailfold microscopy,<br /><br>immunological markers in skin and blood, cardiac MR and 18FDG-PET. The CRISS at<br /><br>12 months. Safety and tolerability outcomes according to CTC-criteria (CTCAE<br /><br>v5.0). Patient reported outcomes at 12 and 24 months include: Quality of life<br /><br>(EQ-5D), SHAQ, Gastrointestinal complaints (GIT 2.0), sexual functioning. </p><br>