Clincosm LogoSign in Get a demo

AST-MOMA: Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis

Sponsor
University Hospital Tuebingen (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01895244
Collaborator
(none)
44
Enrollment
1
Location
2
Arms
144
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
44 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Highdose Chemotherapy and Transplantation of 34+ Selected Stem Cell for Progressive Systemic Sclerosis - Modification According to Manifestation
Actual Study Start Date :
Sep 1, 2012
Actual Primary Completion Date :
Sep 1, 2021
Anticipated Study Completion Date :
Sep 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Efficay - Overall survival [3 years]

    Number of patients that are alive after 3 years

Secondary Outcome Measures

  1. Safety - Treatment related mortality [100 days]

    Treatment related mortality: number of patients who die during the first 100 days after transplantation

  2. Time to engraftment [2 months]

    Time in days from day 0 to platelet count > 20.000 and granulocytes >500/µl

  3. Progression free survival [3 years]

    Time after transplantation without symptoms of disease activity

  4. Efficacy - Lung function test and Skin [3 years]

    Number of patients that achieve either improvement of >25% in mRSS or > 10% in FVC or DLCO

Other Outcome Measures

  1. Efficacy - Patient reported outcome [3 years]

    Differences in Health Assessment Questionnaire (HAQ)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 University Hospital Tuebingen; Department of oncology, hematology, rheumatology, immunology and pulmology Tuebingen Germany 72076

Sponsors and Collaborators

  • University Hospital Tuebingen

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Joerg Henes, Dr. med. Joerg Henes, University Hospital Tuebingen
ClinicalTrials.gov Identifier:
NCT01895244
Other Study ID Numbers:
  • AST MOMA
First Posted:
Jul 10, 2013
Last Update Posted:
May 23, 2022
Last Verified:
May 1, 2022
Keywords provided by Joerg Henes, Dr. med. Joerg Henes, University Hospital Tuebingen
scleroderma
autologous stem cell transplantation
thiotepa
cluster of differentiation (CD) 34 selection
Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse

Study Results

No Results Posted as of May 23, 2022