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Treatment of Refractory Sever Systemic Scleroderma by Injection of Allogeneic Mesenchymal Stem Cells (MSC)

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ClinicalTrials.gov Identifier: NCT02213705
Recruitment Status : Recruiting
First Posted : August 11, 2014
Last Update Posted : April 18, 2016
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
The main ailm of this phase I-II study is to evaluate toxicity and efficacy of allogenic mesenchymal stem cell therapy to treat severe systemic sclerosis. In practice this treatment will be given to patients with a rapidly evolutive disease or refractory to cyclophosphamide.

Condition or disease Intervention/treatment Phase
SYSTEMIC SCLERODERMA ALLOGENEIC MESENCHYMAL STEM CELLS ADULT Biological: INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Refractory Sever Systemic Scleroderma by Injection of Allogeneic Mesenchymal Stem Cells
Study Start Date : June 2014
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS
Administration of allogeneic MSCs in the treatment of severe diffuse SSc or rapidly progressive and refractory to conventional treatments by prior cyclophosphamide
Biological: INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS



Primary Outcome Measures :
  1. toxicity [ Time Frame: 2 years ]

    All grade 3 or above toxicity base on the CTCAE - Cancer Therapy Evaluation Program (CTEP), observed during the 2 years of follow up.

    (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf)



Secondary Outcome Measures :
  1. survival [ Time Frame: 2 years ]
  2. progression free survival [ Time Frame: 2 years ]
  3. Rodnan score [ Time Frame: 2 years ]
  4. Clinical response [ Time Frame: 3, 6, 9, 12 months ]
    Observed clinical response and efficiency in the scalability of SSc: 3, 6, 9 and 12 months after the procedure.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age> 18 years and <70 years.
  • Established diagnosis of systemic sclerosis according to the criteria of the American College of Rheumatology
  • SSc of poor prognosis, involving life-threatening with sever visceral impairment (cardiac, pulmonary or renal) AND " a) contraindicating the use of or b) resistant to " immunosuppressive therapy conventionally used in severe forms of the disease according to the European recommendations of EUSTAR (www.eustar.org) and EBMT (www.ebmt.org) which then rely on high doses of iv cyclophosphamide (either in monthly bolus at least six months or by intensification and autograft of Hematopoietic Stem Cells) or SSc with fibrosing lung damage threatening the vital prognosis which excludes a lung transplant.

These forms of severe and serious SSc WITH at least 6 months follow-up after completion of prior immunosuppressive therapy by high doses of iv cyclophosphamide when they were made, combine to varying degrees : rapidly progressive skin lesions with a score of Rodnan> 15 and one or more of the major visceral lesions defined as follows :

  1. Respiratory disease :

    DLCO <60% or FVC ≤70% of the theoretical value and the presence of interstitial lung disease (abnormalities on chest radiograph and / or lung HRCT with thin sections). It is necessary to ensure that non-related etiologies to scleroderma were eliminated; example: obstructive lung disease (chronic obstructive pulmonary disease or pulmonary emphysema). If the fibrosing lung disease threatens the vital prognosis, we will ensure of the exclusion of a possible lung transplant.

    And/or

  2. Heart disease:

congestive heart failure reversible, ventricular or atrial rhythm disturbances defined as recurrent episodes of atrial fibrillation or atrial flutter, recurrent paroxysmal atrial tachycardia or ventricular tachycardia, atrioventricular block of second or third degree, pericardial effusion with high abundance needing specific treatment of medical type (introduction of steroids) or surgical type (drainage). It is necessary to ensure that non-related etiologies to scleroderma were removed.

  • Signed informed consent.
  • Presence of a consenting intrafamilial MSC donor
  • Affiliation to social security.

Exclusion Criteria:

  • Pregnancy or absence of appropriate contraception throughout the study.
  • Respiratory Disease:
  • systolic Pulmonary arterial pressure (PASP)>55mmHg (on echocardiography or after right heart catheterization);
  • DLCO <30% of the theorical ;
  • Respiratory failure defined by oxygen arterial pressure at rest (PaO2) <8 kPa (<60 mmHg) and / or a blood pressure of carbon dioxide at rest (PaCO2)> 6.7 kPa (> 50 mmHg) without oxygen therapy.

Renal Disease:

  • Calculated creatinine clearance <20 ml/mn/m2
  • Sequelae cystopathy post treatment by cyclophosphamide
  • Heart disease:
  • Clinical sign of a congestive heart failure refractory ;
  • Left ventricular ejection fraction <35% at myocardial scintigraphy or echocardiography;
  • Pulmonary arterial hypertension confirmed by right catheterization or suspected pulmonary hypertension with systolic PAP at echography > 40 mmHg
  • Chronic atrial fibrillation requiring oral anticoagulant therapy;
  • Uncontrolled ventricular arrhythmia;
  • Pericardial effusion with hemodynamic compromise assessed by echocardiography.
  • Hepatic Disease:
  • Hepatic impairment defined as a persistent increase in transaminases or bilirubin to 3 times normal.
  • Psychiatric disorders, including drug taking and alcohol abuse.
  • Active neoplasia or concomitant myelodysplasia, antecedent of neoplasia.
  • Bone marrow failure defined by neutropenia <0.5 x 109 / L, thrombocytopenia <50 x 109 / L, anemia <8 g / dL, CD4 lymphopenia <200 x 106 / L.
  • Uncontrolled systemic hypertension.
  • Uncontrolled acute or chronic infection, HIV1, 2 or HTLV-1, 2seropositivity.
  • Chronic hepatitis B or C active.
  • Significant exposure to bleomycin, toxic oils, vinyl chloride, trichloroethylene or silica; eosinophilia-myalgia syndrome, eosinophilia fasciitis.
  • Risk of poor patient compliance.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02213705


Contacts
Contact: Dominique Farge, MD PHD +33 1 42 49 97 68 dominique.farge-bancel@sls.aphp.fr
Contact: matthieu resche-rigon, MD PHD +33 1 42 49 97 42 matthieu.resche-rigon@paris7.jussieu.fr

Locations
France
Saint-Louis Hospital Recruiting
Paris, France, 75010
Contact: dominique farge, MD PHD    + 33 142499768    dominique.farge-bancel@sls.aphp.fr   
Contact: Chen Wu    + 33 142499768    chen.wu.tec@gmail.com   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: dominique farges, MDPHD APHP

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02213705     History of Changes
Other Study ID Numbers: MSC Severe Systemic Sclerosis
First Posted: August 11, 2014    Key Record Dates
Last Update Posted: April 18, 2016
Last Verified: April 2016

Keywords provided by Assistance Publique - Hôpitaux de Paris:
SYSTEMIC SCLERODERMA
TRANSPLANTATION
ALLOGENEIC MESENCHYMAL STEM CELLS
ADULT

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Connective Tissue Diseases
Skin Diseases