Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis

NCT01895244 | Completed Phase 2 DMC

• 1 other identifier: AST MOMA
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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

Keywords

scleroderma; autologous stem cell transplantation; thiotepa; cluster of differentiation (CD) 34 selection

Outcome Measures

Primary Outcomes (1)

• Efficay - Overall survival

  Number of patients that are alive after 3 years

  3 years

Secondary Outcomes (4)

• Safety - Treatment related mortality

  100 days

• Time to engraftment

  2 months

• Progression free survival

  3 years

• Efficacy - Lung function test and Skin

  3 years

Other Outcomes (1)

• Efficacy - Patient reported outcome

  3 years

Study Arms (2)

Conditioning with CYC/ antithymocyte globulin (ATG)

EXPERIMENTAL

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

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

Conditioning with CYC/Thiotepa/ATG

EXPERIMENTAL

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

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

Interventions

Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells 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/ antithymocyte globulin (ATG); Conditioning with CYC/Thiotepa/ATG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

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

Tübingen, 72076, Germany

Location

Related Publications (1)

• 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.

  PMID: 24459219 DERIVED

MeSH Terms

Conditions

Scleroderma, Diffuse

Interventions

Antigens, Differentiation

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Joerg C Henes, MD

  University Hospital Tuebingen, Department of oncology, hematology, rheumatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. med. Joerg Henes

Study Record Dates

• First Submitted: July 1, 2013
• First Posted: July 10, 2013
• Study Start: September 1, 2012
• Primary Completion: September 1, 2021
• Study Completion: June 1, 2024
• Last Updated: July 29, 2024

Record last verified: 2024-07

Locations

DE (1)