Stem cell transplantation in diffuse cutaneous systemic sclerosis: upfront therapy or rescue therapy after failure of immunosuppressants

Phase 1

Active, not recruiting

• Conditions: Diffuse cutaneous systemic sclerosis according to the ACR/EULAR criteria; MedDRA version: 20.0Level: SOCClassification code: 10021428Term: Immune system disorders Class: 4; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: CTIS2023-505877-34-00
• Lead Sponsor: niversity Medical Center Utrecht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-06-23
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

Age between 18 and 65 years., Fulfilling the 2013 ACR-EULAR classification criteria, Disease duration = 3 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, OR Disease duration = 1 year and diffuse cutaneous disease with mRSS>10 and high risk ANA for organ based disease and/or acute phase response

Exclusion Criteria

Pregnancy or unwillingness to use adequate contraception during study, concomitant severe disease (respiratory, renal, cardiac, liver failure, psychiatric disorders, concurrent neoplasms or myelodysplasia, bone marrow insufficiency, uncontrolled hypertension, uncontrolled acute or chronic infection, ZUBROD-ECOG-WHO PSS > 2, known hypersensitivity to any of the study drug constituents), Previous treatments with immunosuppressants > 12 months including MMF, methotrexate, azathioprine, rituximab, tocilizumab, glucocorticosteroids., Previous treatments with TLI, TBI or alkylating agents including CYC., Significant exposure to bleomycin, tainted rapeseed oil, vinyl chloride, trichlorethylene or silica, eosinophilic myalgia syndrome; eosinophilic fasciitis, 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

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the optimal treatment strategy in early dcSSc: the effect of HSCT as upfront therapy compared with that of immunosuppressive medication in early dcSSc, with respect to survival and prevention of major organ failure (reflected in the Global Rank Composite Score, the primary endpoint).;Secondary Objective: To evaluate (in both treatment arms) whether disease activity correlates with immunological parameters, including immunopathology of skin, immune reconstitution, and autoantibodies. We will also determine the cost-effectiveness of HSCT as first line treatment versus usual care and try to identify factors associated with response to treatment., Safety, Impact on skin thickening, visceral involvement, functional status, sexual functioning and quality of life, cost-effectiveness;Primary end point(s): Global Rank Composite Score (GRCS); an analytic tool that accounts for multiple disease manifestations simultaneously