Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis

NCT ID: NCT01895244

Last Updated: 2024-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2024-06-30

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.

Conditions

Scleroderma; Cardiac Involvement; Autologous Stem Cell Transplantation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Conditioning with CYC/ antithymocyte globulin (ATG)

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

Group Type: EXPERIMENTAL

Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells

Intervention Type: DRUG

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

Conditioning with CYC/Thiotepa/ATG

In patients with cardiac manifestations as defined in the protocol the conditioning for stem cell transplantation is changed to Cyclophosphamide (CYC), thiotepa and ATG

Group Type: EXPERIMENTAL

Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Joerg Henes

Dr. med. Joerg Henes

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joerg C Henes, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tuebingen, Department of oncology, hematology, rheumatology

Locations

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

Tübingen, , Germany

Countries

Germany

References

Henes JC, Koetter I, Horger M, Schmalzing M, Mueller K, Eick C, Bauer A, Vogel W, Kanz L. Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations. Rheumatology (Oxford). 2014 May;53(5):919-22. doi: 10.1093/rheumatology/ket464. Epub 2014 Jan 22.

Reference Type: DERIVED

PMID: 24459219 (View on PubMed)

Other Identifiers

AST MOMA

Identifier Type: -

Identifier Source: org_study_id