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

Primary Purpose

Scleroderma, Cardiac Involvement, Autologous Stem Cell Transplantation

Status
Active
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Scleroderma focused on measuring scleroderma, autologous stem cell transplantation, thiotepa, cluster of differentiation (CD) 34 selection

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Conditioning with CYC/ antithymocyte globulin (ATG)

Conditioning with CYC/Thiotepa/ATG

Arm Description

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

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

Outcomes

Primary Outcome Measures

Efficay - Overall survival
Number of patients that are alive after 3 years

Secondary Outcome Measures

Safety - Treatment related mortality
Treatment related mortality: number of patients who die during the first 100 days after transplantation
Time to engraftment
Time in days from day 0 to platelet count > 20.000 and granulocytes >500/µl
Progression free survival
Time after transplantation without symptoms of disease activity
Efficacy - Lung function test and Skin
Number of patients that achieve either improvement of >25% in mRSS or > 10% in FVC or DLCO

Full Information

First Posted
July 1, 2013
Last Updated
May 16, 2022
Sponsor
University Hospital Tuebingen
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1. Study Identification

Unique Protocol Identification Number
NCT01895244
Brief Title
Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis
Acronym
AST-MOMA
Official Title
Highdose Chemotherapy and Transplantation of 34+ Selected Stem Cell for Progressive Systemic Sclerosis - Modification According to Manifestation
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 2012 (Actual)
Primary Completion Date
September 2021 (Actual)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Tuebingen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Scleroderma, Cardiac Involvement, Autologous Stem Cell Transplantation
Keywords
scleroderma, autologous stem cell transplantation, thiotepa, cluster of differentiation (CD) 34 selection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Conditioning with CYC/ antithymocyte globulin (ATG)
Arm Type
Experimental
Arm Description
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
Arm Title
Conditioning with CYC/Thiotepa/ATG
Arm Type
Experimental
Arm Description
In patients with cardiac manifestations as defined in the protocol the conditioning for stem cell transplantation is changed to Cyclophosphamide (CYC), thiotepa and ATG
Intervention Type
Drug
Intervention Name(s)
Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells
Intervention Description
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
Primary Outcome Measure Information:
Title
Efficay - Overall survival
Description
Number of patients that are alive after 3 years
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Safety - Treatment related mortality
Description
Treatment related mortality: number of patients who die during the first 100 days after transplantation
Time Frame
100 days
Title
Time to engraftment
Description
Time in days from day 0 to platelet count > 20.000 and granulocytes >500/µl
Time Frame
2 months
Title
Progression free survival
Description
Time after transplantation without symptoms of disease activity
Time Frame
3 years
Title
Efficacy - Lung function test and Skin
Description
Number of patients that achieve either improvement of >25% in mRSS or > 10% in FVC or DLCO
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Efficacy - Patient reported outcome
Description
Differences in Health Assessment Questionnaire (HAQ)
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joerg C Henes, MD
Organizational Affiliation
University Hospital Tuebingen, Department of oncology, hematology, rheumatology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Tuebingen; Department of oncology, hematology, rheumatology, immunology and pulmology
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
24459219
Citation
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.
Results Reference
derived

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Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis

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