<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02213705</url>
  </required_header>
  <id_info>
    <org_study_id>MSC Severe Systemic Sclerosis</org_study_id>
    <nct_id>NCT02213705</nct_id>
  </id_info>
  <brief_title>Treatment of Refractory Sever Systemic Scleroderma by Injection of Allogeneic Mesenchymal Stem Cells</brief_title>
  <acronym>MSC</acronym>
  <official_title>Treatment of Refractory Sever Systemic Scleroderma by Injection of Allogeneic Mesenchymal Stem Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <brief_summary>
    <textblock>
      The main ailm of this phase I-II study is to evaluate toxicity and efficacy of allogenic&#xD;
      mesenchymal stem cell therapy to treat severe systemic sclerosis. In practice this treatment&#xD;
      will be given to patients with a rapidly evolutive disease or refractory to cyclophosphamide.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 6, 2014</start_date>
  <completion_date type="Actual">June 16, 2022</completion_date>
  <primary_completion_date type="Actual">February 9, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Immediate Toxicity</measure>
    <time_frame>10 days</time_frame>
    <description>Immediate Toxicity/tolerance defined as grade 3 or above toxicity base on the CTCAE - Cancer Therapy Evaluation Program (CTEP), observed during the first 10 days (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Medium-term tolerance</measure>
    <time_frame>2 years</time_frame>
    <description>Treatment-related event-free survival at 2 years. Treatment-related event (morbidity) being defined by the onset of clinical events induced by the procedure and not explained by the natural or expected course of the scleroderma disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>2 years</time_frame>
    <description>Time from inclusion to death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>2 years</time_frame>
    <description>Defined as the time in days from the day of inclusion until the occurrence of changes compared to the initial assessment, documented and re-evaluated at two successive examinations 3 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CBC</measure>
    <time_frame>1, 2, 3, 4, 8, 12, 16, 20, 24 weeks</time_frame>
    <description>complete blood count (CBC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet</measure>
    <time_frame>1, 2, 3, 4, 8, 12, 16, 20, 24 weeks</time_frame>
    <description>Platelet blood count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lymphocyte</measure>
    <time_frame>3, 6, 9, 12, 15, 18, 24 months</time_frame>
    <description>Lymphocyte subpopulation blood count measured by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody</measure>
    <time_frame>3, 6, 9, 12, 15, 18, 24 months</time_frame>
    <description>Antibody response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rodnan score</measure>
    <time_frame>3, 6, 9, 12, 15, 18, 24 months</time_frame>
    <description>modified Rodnan Score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SHAQ</measure>
    <time_frame>3, 6, 9, 12, 15, 18, 24 months</time_frame>
    <description>Scleroderma Health Assessment Questionnaire (SHAQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical progression</measure>
    <time_frame>3, 6, 9, 12, 15, 18, 24 months</time_frame>
    <description>Occurence of visceral involvement, defined as any of the following:&#xD;
Pulmonary: diffusion capacity of CO (DLCO and DLCO/VA), forced vital capacity (FVC), total lung capacity (TLC), residual volume (RV), pulmonary artery pressure (measured by echocardiography or right heart catheterisation), arterial blood gases (pO2, pCO2, p(A-a)O2) in ambient air,&#xD;
Myocardial: ECG, left ventricular function measured by echocardiography (and cardiac MRI and/or Gating in the event of cardiac abnormality or suspected LV dysfunction on ultrasound) with semi-quantitative analysis of the degree of cardiac damage according to the cardiac score (based on the presence or absence of left axial deviation on the electrocardiogram and/or moderate or significant pericardial effusion according to the echocardiogram),&#xD;
Renal: 24-hour proteinuria, creatinine clearance,&#xD;
Patient's weight in kg,</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical response</measure>
    <time_frame>3, 6, 9, 12, 15, 18, 24 months</time_frame>
    <description>Defined by a 25% improvement in modified Rodnan Score and/or ≥10% in DLCO or FVC compared to baseline state without the need to reintroduce other immunosuppressants.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>SYSTEMIC SCLERODERMA</condition>
  <condition>ALLOGENEIC MESENCHYMAL STEM CELLS</condition>
  <condition>ADULT</condition>
  <arm_group>
    <arm_group_label>INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of allogeneic MSCs in the treatment of severe diffuse SSc or rapidly progressive and refractory to conventional treatments by prior cyclophosphamide</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS</intervention_name>
    <arm_group_label>INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age&gt; 18 years and &lt;70 years.&#xD;
&#xD;
          -  Established diagnosis of systemic sclerosis according to the criteria of the American&#xD;
             College of Rheumatology&#xD;
&#xD;
          -  SSc of poor prognosis, involving life-threatening with sever visceral impairment&#xD;
             (cardiac, pulmonary or renal) AND &quot; a) contraindicating the use of or b) resistant to&#xD;
             &quot; immunosuppressive therapy conventionally used in severe forms of the disease&#xD;
             according to the European recommendations of EUSTAR (www.eustar.org) and EBMT&#xD;
             (www.ebmt.org) which then rely on high doses of iv cyclophosphamide (either in monthly&#xD;
             bolus at least six months or by intensification and autograft of Hematopoietic Stem&#xD;
             Cells) or SSc with fibrosing lung damage threatening the vital prognosis which&#xD;
             excludes a lung transplant.&#xD;
&#xD;
        These forms of severe and serious SSc WITH at least 6 months follow-up after completion of&#xD;
        prior immunosuppressive therapy by high doses of iv cyclophosphamide when they were made,&#xD;
        combine to varying degrees : rapidly progressive skin lesions with a score of Rodnan&gt; 15&#xD;
        and one or more of the major visceral lesions defined as follows :&#xD;
&#xD;
          1. Respiratory disease :&#xD;
&#xD;
             DLCO &lt;60% or FVC ≤70% of the theoretical value and the presence of interstitial lung&#xD;
             disease (abnormalities on chest radiograph and / or lung HRCT with thin sections). It&#xD;
             is necessary to ensure that non-related etiologies to scleroderma were eliminated;&#xD;
             example: obstructive lung disease (chronic obstructive pulmonary disease or pulmonary&#xD;
             emphysema). If the fibrosing lung disease threatens the vital prognosis, we will&#xD;
             ensure of the exclusion of a possible lung transplant.&#xD;
&#xD;
             And/or&#xD;
&#xD;
          2. Heart disease:&#xD;
&#xD;
        congestive heart failure reversible, ventricular or atrial rhythm disturbances defined as&#xD;
        recurrent episodes of atrial fibrillation or atrial flutter, recurrent paroxysmal atrial&#xD;
        tachycardia or ventricular tachycardia, atrioventricular block of second or third degree,&#xD;
        pericardial effusion with high abundance needing specific treatment of medical type&#xD;
        (introduction of steroids) or surgical type (drainage). It is necessary to ensure that&#xD;
        non-related etiologies to scleroderma were removed.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
          -  Presence of a consenting intrafamilial MSC donor&#xD;
&#xD;
          -  Affiliation to social security.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or absence of appropriate contraception throughout the study.&#xD;
&#xD;
          -  Respiratory Disease:&#xD;
&#xD;
          -  systolic Pulmonary arterial pressure (PASP)&gt;55mmHg (on echocardiography or after right&#xD;
             heart catheterization);&#xD;
&#xD;
          -  DLCO &lt;30% of the theorical ;&#xD;
&#xD;
          -  Respiratory failure defined by oxygen arterial pressure at rest (PaO2) &lt;8 kPa (&lt;60&#xD;
             mmHg) and / or a blood pressure of carbon dioxide at rest (PaCO2)&gt; 6.7 kPa (&gt; 50 mmHg)&#xD;
             without oxygen therapy.&#xD;
&#xD;
        Renal Disease:&#xD;
&#xD;
          -  Calculated creatinine clearance &lt;20 ml/mn/m2&#xD;
&#xD;
          -  Sequelae cystopathy post treatment by cyclophosphamide&#xD;
&#xD;
          -  Heart disease:&#xD;
&#xD;
          -  Clinical sign of a congestive heart failure refractory ;&#xD;
&#xD;
          -  Left ventricular ejection fraction &lt;35% at myocardial scintigraphy or&#xD;
             echocardiography;&#xD;
&#xD;
          -  Pulmonary arterial hypertension confirmed by right catheterization or suspected&#xD;
             pulmonary hypertension with systolic PAP at echography &gt; 40 mmHg&#xD;
&#xD;
          -  Chronic atrial fibrillation requiring oral anticoagulant therapy;&#xD;
&#xD;
          -  Uncontrolled ventricular arrhythmia;&#xD;
&#xD;
          -  Pericardial effusion with hemodynamic compromise assessed by echocardiography.&#xD;
&#xD;
          -  Hepatic Disease:&#xD;
&#xD;
          -  Hepatic impairment defined as a persistent increase in transaminases or bilirubin to 3&#xD;
             times normal.&#xD;
&#xD;
          -  Psychiatric disorders, including drug taking and alcohol abuse.&#xD;
&#xD;
          -  Active neoplasia or concomitant myelodysplasia, antecedent of neoplasia.&#xD;
&#xD;
          -  Bone marrow failure defined by neutropenia &lt;0.5 x 109 / L, thrombocytopenia &lt;50 x 109&#xD;
             / L, anemia &lt;8 g / dL, CD4 lymphopenia &lt;200 x 106 / L.&#xD;
&#xD;
          -  Uncontrolled systemic hypertension.&#xD;
&#xD;
          -  Uncontrolled acute or chronic infection, HIV1, 2 or HTLV-1, 2seropositivity.&#xD;
&#xD;
          -  Chronic hepatitis B or C active.&#xD;
&#xD;
          -  Significant exposure to bleomycin, toxic oils, vinyl chloride, trichloroethylene or&#xD;
             silica; eosinophilia-myalgia syndrome, eosinophilia fasciitis.&#xD;
&#xD;
          -  Risk of poor patient compliance.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>dominique farges, MDPHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>APHP</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Saint-Louis Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SYSTEMIC SCLERODERMA</keyword>
  <keyword>TRANSPLANTATION</keyword>
  <keyword>ALLOGENEIC MESENCHYMAL STEM CELLS</keyword>
  <keyword>ADULT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scleroderma, Systemic</mesh_term>
    <mesh_term>Scleroderma, Diffuse</mesh_term>
    <mesh_term>Scleroderma, Localized</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02213705
org study id: MSC Severe Systemic Sclerosis
nct id: NCT02213705
lead sponsor: 
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Immediate Toxicity
time frame: 10 days
description: Immediate Toxicity/tolerance defined as grade 3 or above toxicity base on the CTCAE - Cancer Therapy Evaluation Program (CTEP), observed during the first 10 days (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf)
measure: Medium-term tolerance
time frame: 2 years
description: Treatment-related event-free survival at 2 years. Treatment-related event (morbidity) being defined by the onset of clinical events induced by the procedure and not explained by the natural or expected course of the scleroderma disease.
measure: Survival
time frame: 2 years
description: Time from inclusion to death
measure: Progression free survival
time frame: 2 years
description: Defined as the time in days from the day of inclusion until the occurrence of changes compared to the initial assessment, documented and re-evaluated at two successive examinations 3 months
measure: CBC
time frame: 1, 2, 3, 4, 8, 12, 16, 20, 24 weeks
description: complete blood count (CBC)
measure: Platelet
time frame: 1, 2, 3, 4, 8, 12, 16, 20, 24 weeks
description: Platelet blood count
measure: Lymphocyte
time frame: 3, 6, 9, 12, 15, 18, 24 months
description: Lymphocyte subpopulation blood count measured by flow cytometry
measure: Antibody
time frame: 3, 6, 9, 12, 15, 18, 24 months
description: Antibody response
measure: Rodnan score
time frame: 3, 6, 9, 12, 15, 18, 24 months
description: modified Rodnan Score
measure: SHAQ
time frame: 3, 6, 9, 12, 15, 18, 24 months
description: Scleroderma Health Assessment Questionnaire (SHAQ)
measure: Clinical progression
time frame: 3, 6, 9, 12, 15, 18, 24 months
description: Occurence of visceral involvement, defined as any of the following:
Pulmonary: diffusion capacity of CO (DLCO and DLCO/VA), forced vital capacity (FVC), total lung capacity (TLC), residual volume (RV), pulmonary artery pressure (measured by echocardiography or right heart catheterisation), arterial blood gases (pO2, pCO2, p(A-a)O2) in ambient air,
Myocardial: ECG, left ventricular function measured by echocardiography (and cardiac MRI and/or Gating in the event of cardiac abnormality or suspected LV dysfunction on ultrasound) with semi-quantitative analysis of the degree of cardiac damage according to the cardiac score (based on the presence or absence of left axial deviation on the electrocardiogram and/or moderate or significant pericardial effusion according to the echocardiogram),
Renal: 24-hour proteinuria, creatinine clearance,
Patient's weight in kg,
measure: Clinical response
time frame: 3, 6, 9, 12, 15, 18, 24 months
description: Defined by a 25% improvement in modified Rodnan Score and/or ≥10% in DLCO or FVC compared to baseline state without the need to reintroduce other immunosuppressants.
arm group label: INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS
arm group type: Experimental
description: Administration of allogeneic MSCs in the treatment of severe diffuse SSc or rapidly progressive and refractory to conventional treatments by prior cyclophosphamide
intervention type: Biological
intervention name: INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS
arm group label: INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: dominique farges, MDPHD
role: Principal Investigator
affiliation: APHP
facility: 
country: France
responsible party type: Sponsor
mesh term: Scleroderma, Systemic
mesh term: Scleroderma, Diffuse
mesh term: Scleroderma, Localized