Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis

Scleroderma Clinical Trial

— AST-MOMA  

Official title:

Highdose Chemotherapy and Transplantation of 34+ Selected Stem Cell for Progressive Systemic Sclerosis - Modification According to Manifestation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01895244
• Other study ID #: AST MOMA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 2012
• Est. completion date: September 2024

Study information

• Verified date: May 2022
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 44
• Est. completion date: September 2024
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Autologous Stem Cell Transplantation
• Cardiac Involvement
• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Systemic

Intervention

Drug:
• Autologous 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

Locations

Country	Name	City	State
Germany	University Hospital Tuebingen; Department of oncology, hematology, rheumatology, immunology and pulmology	Tuebingen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Efficacy - Patient reported outcome	Differences in Health Assessment Questionnaire (HAQ)	3 years
Primary	Efficay - Overall survival	Number of patients that are alive after 3 years	3 years
Secondary	Safety - Treatment related mortality	Treatment related mortality: number of patients who die during the first 100 days after transplantation	100 days
Secondary	Time to engraftment	Time in days from day 0 to platelet count > 20.000 and granulocytes >500/µl	2 months
Secondary	Progression free survival	Time after transplantation without symptoms of disease activity	3 years
Secondary	Efficacy - Lung function test and Skin	Number of patients that achieve either improvement of >25% in mRSS or > 10% in FVC or DLCO	3 years