Autologous Stem Cell Transplantation, Cardiac Involvement, Scleroderma
Conditions
Keywords
scleroderma, autologous stem cell transplantation, thiotepa, cluster of differentiation (CD) 34 selection
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.
Interventions
DRUGAutologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells
If no active alveolitis: mobilisation with 2x1g Cyclophosphamide If active alveolitis: mobilisation with 2x1.5g Cyclophosphamid If cardiac manifestation: Conditioning with CYC 2 x 50mg + thiotepa 2x5mg + ATG If no cardiac manifestation: Conditioning with 4 x 50mg CYC + ATG
Sponsors
University Hospital Tuebingen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficay - Overall survival | 3 years | Number of patients that are alive after 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Treatment related mortality | 100 days | Treatment related mortality: number of patients who die during the first 100 days after transplantation |
| Time to engraftment | 2 months | Time in days from day 0 to platelet count \> 20.000 and granulocytes \>500/µl |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Efficacy - Patient reported outcome | 3 years | Differences in Health Assessment Questionnaire (HAQ) |
Countries
Germany
Outcome results
None listed