Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis (AST-MOMA)

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Tuebingen, Germany, 72076
    • University Hospital Tuebingen; Department of oncology, hematology, rheumatology, immunology and pulmology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	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
Experimental: 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	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficay - Overall survival	Number of patients that are alive after 3 years	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Treatment related mortality	Treatment related mortality: number of patients who die during the first 100 days after transplantation	100 days
Time to engraftment	Time in days from day 0 to platelet count > 20.000 and granulocytes >500/µl	2 months
Progression free survival	Time after transplantation without symptoms of disease activity	3 years
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy - Patient reported outcome	Differences in Health Assessment Questionnaire (HAQ)	3 years

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Joerg C Henes, MD, University Hospital Tuebingen, Department of oncology, hematology, rheumatology

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): June 1, 2024

Study Registration Dates

• First Submitted: July 1, 2013
• First Submitted That Met QC Criteria: July 4, 2013
• First Posted (Estimated): July 10, 2013

Study Record Updates

• Last Update Posted (Actual): July 29, 2024
• Last Update Submitted That Met QC Criteria: July 26, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: scleroderma; autologous stem cell transplantation; thiotepa; cluster of differentiation (CD) 34 selection
• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: AST MOMA