Upfront Autologous HSCT Versus Immunosuppression in Early Diffuse Cutaneous Systemic Sclerosis

Summary

HSCT has been implemented in (inter)national treatment guidelines for diffuse cutaneous systemic sclerosis (dcSSc) and is offered in clinical care and reimbursed by national health insurance in several European countries. However, data and specific guidelines on the best timing of HSCT in the course of dcSSc are lacking. In particular, it is unclear whether HSCT should be positioned as upfront therapy or as rescue treatment for patients not responding to conventional immunosuppressive therapy.

This multicentre, randomized, open label trial aims to compare two treatment strategies used in usual care: upfront autologous HSCT versus usual care with (intravenous (i.v.) cyclophosphamide (CYC) pulse therapy followed by mycophenolate mofetil (MMF) and HSCT as rescue option).

Conditions

• Systemic Sclerosis
• Systemic Scleroses, Diffuse
• Scleroderma
• Scleroderma, Diffuse
• Autologous Stem Cell Transplantation
• Cyclophosphamide
• Mycophenolate Mofetil
• Treatment Strategy

Interventions

PROCEDURE

Upfront autologous HSCT

HSCT comprises the following consecutive steps: 1. Mobilisation * Infusions of CYC 2g/m2 on 1 day. * Hyperhydration, alkalinisation of urine and mesna to prevent haemorrhagic cystitis. * Filgrastim (G-CSF) 5-10 μg/kg/day subcutaneously for 5 days (or more when necessary). 2. Leukapheresis Prompt start of leukapheresis is required at a CD34+ cell count of ≥10-20/μL. Goal: at least 2 x 10\^6 CD34+ cells per kilogram body weight. 3. Conditioning * CYC 50 mg/kg/day intravenously for 4 consecutive days (total 200 mg/kg) * Rabbit Antithymocyte Globulin (rbATG), a total dose of 7.5 mg/kg i.v., from Genzyme. Hyperhydration, alkalinisation of the urine and mesna will be given to prevent haemorrhagic cystitis. I.v. methylprednisolone 2 mg/kg will be administered on the days ATG, to improve tolerability of the ATG. 4. Peripheral stem cell infusion The number of CD34+ cells to be reinfused should be ≥ 2.0 x 10\^6/kg.

Sponsors & Collaborators

• ZonMw: The Netherlands Organisation for Health Research and Development

  collaborator OTHER

• Boehringer Ingelheim

  collaborator INDUSTRY

• Miltenyi Biotec, Inc.

  collaborator INDUSTRY

• UMC Utrecht

  lead OTHER

Principal Investigators

• Jacob M van Laar, MD PhD · UMC Utrecht

• Julia Spierings · UMC Utrecht

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-09-17

Primary Completion

2026-03-19

Completion

2026-03-19

Countries

• Italy
• Netherlands
• United Kingdom

Study Locations