Erken Diffüz Kutanöz Sistemik Sklerozda Öncelikli Otolog Kök Hücre Nakli ile İmmünosupresyon Karşılaştırması

Sade dilde özet

Bu çalışma, erken diffüz kutanöz sistemik skleroz (diffuse cutaneous systemic sclerosis) hastalarında öncelikli otolog kök hücre naklini (autologous HSCT) standart bağışıklık baskılayıcı (immünosupresif) tedaviyle karşılaştırmıştır. 18-65 yaş arası, tanı kriterlerini karşılayan ve ilerleyici hastalığı olan kişiler katılıma uygundur. Çalışma Faz 4 aşamasında yürütülmüş ve tamamlanmıştır.

Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.

Deney bilgileri

Faz

Faz 4 (Phase 4)

Durum

Tamamlandı

Sponsor

UMC Utrecht

Müdahale

Upfront autologous HSCT

Başlangıç

17.09.2020

Tahmini bitiş

19.03.2026

Ülkeler

Italy, Netherlands, United Kingdom

İlgili genler

Merkezler

• Milan, Italy
• Milan, Italy
• Roma, Italy
• Amsterdam, Netherlands
• Leiden, Netherlands
• Nijmegen, Netherlands
• Utrecht, Netherlands
• Sheffield, United Kingdom

Uygunluk kriterleri

Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.

Inclusion Criteria:

1. Age between 18 and 65 years.
2. Fulfilling the 2013 ACR-EULAR classification criteria for SSc

   Either: 3.1 or 3.2 3.1. Disease duration ≤ 3 years (from onset of first non-Raynaud's symptoms) and diffuse cutaneous disease with

   \- progressive skin involvement with a mRSS ≥ 15 (in a diffuse pattern: involvement of skin on the upper limbs, chest and/or abdomen)

   and/or

   \- major organ involvement as defined by either:

   a. clinically significant 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 rela-tive 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 ex-cluded, within 12 months. Intercurrent infections excluded.

   b. clinically significant renal involvement = i. new renal insufficiency (serum creatinine \> upper limit of normal) AND
   1. persistent urinalysis abnormalities (proteinuria, haematuria, casts), AND/OR
   2. microangiopathic haemolytic anaemia AND/OR
   3. hypertension (two successive BP readings of either systolic ≥ 160 mm Hg or diastolic \> 110 mm Hg, at least 12 hours apart), ; non-scleroderma related causes (e.g. medication, infection etc.) must be reasonably excluded.

   c. clinically significant cardiac involvement = any of the following criteria: i. reversible congestive heart failure, ii. atrial or ventricular rhythm disturbances such as atrial fibrillation or flutter, atrial paroxysmal tachycar-dia or ventricular tachycardia, 2nd or 3rd degree AV block, iii. pericardial effusion (not leading to hemodynamic problems), myocarditis; non-scleroderma related causes must have been reasonably excluded

   3.2. Disease duration ≤ 1 year (from onset of first non-Raynaud's symptoms) and diffuse cutaneous disease with mRSS ≥ 10 and
   1. High risk ANA for organ based disease: ATA or ARA positivity and/ or
   2. Acute phase response (ESR \> 25 mm/h and/or CRP \> 10.0 mg/L )

4\. Written Informed consent

Exclusion Criteria:

1. Pregnancy or unwillingness to use adequate contraception during study
2. Concomitant severe disease =

   1. respiratory: resting mean pulmonary artery pressure (mPAP) \> 25 mmHg (by right heart catheterisation), DLCO \< 40% predicted, respiratory failure as defined by the primary endpoint
   2. renal: creatinine clearance \< 40 ml/min (measured or estimated)
   3. 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
   4. liver failure as defined by a sustained 3-fold increase in serum transaminase or bilirubin, or a Child-Pugh score C
   5. psychiatric disorders including active drug or alcohol abuse
   6. concurrent neoplasms or myelodysplasia
   7. bone marrow insufficiency defined as leukocytopenia \< 4.0 x 109/L, thrombocytopenia \< 50x 10\^9/L, anaemia \< 8 gr/dL, CD4+ T lymphopenia \< 200 x 106/L
   8. uncontrolled hypertension
   9. uncontrolled acute or chronic infection, including HIV, HTLV-1,2 positivity
   10. ZUBROD-ECOG-WHO Performance Status Scale \> 2
3. Previous treatments with immunosuppressants \> 12 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.