Upfront HSCT versus rescue HSCT in early dcSSc

  • Research type

    Research Study

  • Full title

    Upfront autologous hematopoietic stem cell transplantation versus immunosuppressive medication in early diffuse cutaneous systemic sclerosis: an international multicentre, open-label, randomized controlled trial

  • IRAS ID

    1007511

  • Contact name

    John Snowden

  • Contact email

    john.snowden1@nhs.net

  • Sponsor organisation

    University Medical Centre Utrecht

  • Eudract number

    2019-004718-32

  • Clinicaltrials.gov Identifier

    NCT04464434

  • Research summary

    Diffuse cutaneous systemic sclerosis (dcSSc) is an autoimmune disease with high burden of disease and increased mortality.\nDisease progression can be slowed down with immunosuppressive therapies such as cyclophosphamide (i.v. CYC), mycophenolate mofetil (MMF). Patients who do not respond to such therapies could opt for autologous hematopoietic stem cell transplantion (HSCT). \nHSCT has been used in regular care for 20 years in dcSSc in Europe, Australia, Japan and Canada and has been demonstrated to improve skin and lungs, quality of life and even survival. However, HSCT is also associated with a higher risk of complications and is therefore only chosen when conventional measures have failed.\n\nThe UPSIDE study group hypothesizes that using HSCT earlier in the disease could have fewer risks and may be more effective than later in the disease. The aim of the multicenter, open label, randomized UPSIDE trial is therefore to determine the optimal timing of HSCT in patients with dcSSc. Adult patients who have had SSc for less than 3 years with diffuse skin or organ involvement, can participate.\nPatients who are randomly assigned to study arm A will start with HSCT immediately. \nHSCT consists of three steps: retrieving the patient’s stem cells using chemotherapy and injections with growth factors. Secondly, high dose chemotherapy and anti-thymoglobulin will be administered to eliminate dysregulated immune cells. Next, stem cells will be reinfused and the immune system will recover gradually. \nIn arm B, patients will receive standard of care including monthly i.v. CYC during one year followed with at least one year of MMF. Patients in arm B can receive a rescue HSCT in case of insufficient response.\nThe primary outcome is a the Global Rank Composit Score which includes survival, skin score, lung involvement, daily functioning and quality of life. Other outcomes include safety and daily functioning.

  • REC name

    Yorkshire & The Humber - Leeds West Research Ethics Committee

  • REC reference

    24/YH/0030

  • Date of REC Opinion

    9 Apr 2024

  • REC opinion

    Further Information Favourable Opinion