Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis

Phase 2

Completed

• Conditions: Autologous Stem Cell Transplantation; Cardiac Involvement; Scleroderma
• Interventions: Drug: Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells

• Registration Number: NCT01895244
• Lead Sponsor: University Hospital Tuebingen

Brief Summary

Autologous stem cell therapy has been shown to be effective in patients with systemic sclerosis. Nevertheless treatment is associated with treatment related mortality and patients die during follow up despite successful transplantation.

Intention of this trial is to improve overall survival by modifying the existing protocol used for the ASTIS trial.

To reduce treatment toxicity we reduce the dose of Cyclophosphamide (CYC) for mobilisation to 2x1g.

Especially in patients with cardiac manifestations we also modify the conditioning regimen by adding thiotepa and reducing CYC; as CYC has known cardiotoxic side effects.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-09
• Study First Submitted: 2013-07-01
• Study First Submitted QC: 2013-07-04
• Study First Posted: 2013-07-10
• Primary Completion: 2021-09
• Study Completion: 2024-06
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-26
• Last Update Posted: 2024-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

• Diagnosis of progressive systemic sclerosis <7 years

• Progressive course despite cyclophosphamide pretreatment

• Cyclophosphamide i.v.: at least 3 x with 500-1000 mg/m² every 3-4 weeks or

• Cyclophosphamide p.o. with at least 100mg/day for at least 2 months or

• Contraindication to treatment with cyclophosphamide

• Progress defined as at least one of the following criteria:

  • Increase in the mRSS
  • Worsening of the lung function
  • Increase in fibrosis/alveolitis in thorax CT
  • Worsening kidney function through manifestation of systemic sclerosis

• Limited or diffuse cutaneous progressive form of Ssc with organ manifestation in the lungs/heart or kidneys

Exclusion Criteria

• Age <18 years
• Pregnancy or inadequate contraception
• Severe heart failure with ejection fraction (EF) < 30% in echo
• Pulmonary arterial hypertension with systolic pulmonary arterial pressure (PAPsys) >50mm Hg
• Kidney insufficiency: creatinine clearance <30 ml/min
• Reduced lung function
• Inspiratory vital capacity (IVC) < 50% of normal
• Carbon monoxide (CO)-Diffusion capacity SB < 40%
• Previously damaged bone marrow
• Leukopenia < 2,000/µl
• Thrombopenia < 100,000/µl
• Previous myelotoxic treatment:
• Cyclophosphamide > 50g cumulative (relative)
• Infection (Hepatitis B/C, HIV, Salmonella carrier, syphilis, relative: history of tuberculosis)
• Severe concomitant psychiatric illness (depression, psychosis)
• Substance dependence
• Continued nicotine abuse
• Continued alcohol abuse
• Continued drug abuse
• Consent not given
• Poor compliance

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Conditioning with CYC/ antithymocyte globulin (ATG)	Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells	Each patient receives stem cell transplantation open label with cluster of differentiation (CD)34 selected stem cells mobilisation and conditioning depending on manifestation If cardiac manifestation: Conditioning with CYC 2 x 50mg + thiotepa 2x5mg + ATG If no cardiac manifestation: Conditioning with 4 x 50mg CYC + ATG
Conditioning with CYC/Thiotepa/ATG	Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells	In patients with cardiac manifestations as defined in the protocol the conditioning for stem cell transplantation is changed to Cyclophosphamide (CYC), thiotepa and ATG

Primary Outcome Measures

Name	Time	Method
Efficay - Overall survival	3 years	Number of patients that are alive after 3 years

Secondary Outcome Measures

Name	Time	Method
Safety - Treatment related mortality	100 days	Treatment related mortality: number of patients who die during the first 100 days after transplantation
Progression free survival	3 years	Time after transplantation without symptoms of disease activity
Efficacy - Lung function test and Skin	3 years	Number of patients that achieve either improvement of \>25% in mRSS or \> 10% in FVC or DLCO
Time to engraftment	2 months	Time in days from day 0 to platelet count \> 20.000 and granulocytes \>500/µl

Trial Locations

Locations (1)

University Hospital Tuebingen; Department of oncology, hematology, rheumatology, immunology and pulmology; 🇩🇪 Tuebingen, Germany