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 2014 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 29, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Scleroderma
Cardiac Involvement
Autologous Stem Cell Transplantation
Drug: Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Highdose Chemotherapy and Transplantation of 34+ Selected Stem Cell for Progressive Systemic Sclerosis - Modification According to Manifestation

Resource links provided by NLM:


Further study details as provided by University Hospital Tuebingen:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • Patient reported outcome [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Differences in Health Assessment Questionnaire (HAQ)


Estimated Enrollment: 44
Study Start Date: September 2012
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01895244

Contacts
Contact: Joerg C Henes, MD +4970712982711 joerg.henes@med.uni-tuebingen.de
Contact: Theodoros Xenitidis, MD +4970712982711 theodoros.xenitidis@med.uni-tuebingen.de

Locations
Germany
University Hospital Tuebingen; Department of oncology, hematology, rheumatology, immunology and pulmology Recruiting
Tuebingen, Germany, 72076
Contact: Joerg C Henes, MD    +4970712982711    joerg.henes@med.uni-tuebingen.de   
Sub-Investigator: Theodoros Xenitidis, MD         
Sub-Investigator: Robert Moehle, MD         
Sponsors and Collaborators
University Hospital Tuebingen
Investigators
Principal Investigator: Joerg C Henes, MD University Hospital Tuebingen, Department of oncology, hematology, rheumatology
  More Information

No publications provided by University Hospital Tuebingen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Joerg Henes, Dr. med. Joerg Henes, University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT01895244     History of Changes
Other Study ID Numbers: AST MOMA
Study First Received: July 1, 2013
Last Updated: July 29, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by University Hospital Tuebingen:
scleroderma
autologous stem cell transplantation
thiotepa
cluster of differentiation (CD) 34 selection

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Connective Tissue Diseases
Skin Diseases
Thiotepa
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014