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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University Hospital Tuebingen
Sponsor:
Information provided by (Responsible Party):
Joerg Henes, University Hospital Tuebingen
ClinicalTrials.gov Identifier:
NCT01895244
First received: July 1, 2013
Last updated: July 11, 2013
Last verified: July 2013

July 1, 2013
July 11, 2013
September 2012
September 2017   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01895244 on ClinicalTrials.gov Archive Site
  • Treatment related mortality [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    Treatment related mortality: number of patients who die during the first 100 days after transplantation
  • Time to engraftment [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Time in days from day 0 to platelet count > 20.000 and granulocytes >500/µl
  • Progression free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Time after transplantation without symptoms of disease activity
  • Efficacy [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Reduction of modified Rodnan Skin score (mRSS) after transplantation
  • Treatment related mortality [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    Treatment related mortality: number of patients who die during the first 100 days after transplantation
  • Time to engraftment [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Time in days from day 0 to platelet count > 20.000 and granulocytes >500/µl
  • Progression free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Time after transplantation without symptoms of disease activity
  • Efficacy [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Reduction of modified Rodnan Skin score after transplantation
Patient reported outcome [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Differences in Health Assessment Questionnaire (HAQ)
Patient reported outcome [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Differences in HAQ, FFBh
 
Highdose Chemotherapy and Transplantation of 34+ Selected Stem Cell for Progressive Systemic Sclerosis - Modification According to Manifestation
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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Scleroderma
  • Cardiac Involvement
  • Autologous Stem Cell Transplantation
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/ 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
    Intervention: Drug: Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells
  • 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
    Intervention: Drug: Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
44
September 2020
September 2017   (final data collection date for primary outcome measure)

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 < 30%
  • 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
Both
18 Years to 65 Years
No
Contact: Joerg C Henes, MD +4970712982711 joerg.henes@med.uni-tuebingen.de
Contact: Theodoros Xenitidis, MD +4970712982711 theodoros.xenitidis@med.uni-tuebingen.de
Germany
 
NCT01895244
AST MOMA
Yes
Joerg Henes, University Hospital Tuebingen
University Hospital Tuebingen
Not Provided
Principal Investigator: Joerg C Henes, MD University Hospital Tuebingen, Department of oncology, hematology, rheumatology
University Hospital Tuebingen
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP