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SYSTEMIC SCLERODERMAPhase 1/2MSCNCT02213705

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

A Phase 1/2 study testing INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS in people with SYSTEMIC SCLERODERMA and ALLOGENEIC MESENCHYMAL STEM CELLS, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteFrance
Study dates
6 May 2014to 16 Jun 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 :
  • 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.
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  • And/or
  • 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.

Who cannot join

  • 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:
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  • 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.

Trial locations and contacts

1 site in 1 country.

France1 site

  • Saint-Louis Hospital

    Paris, 75010

Other trials in France

About this study

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.

Being tested
INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS
Keywords
SYSTEMIC SCLERODERMA, TRANSPLANTATION, ALLOGENEIC MESENCHYMAL STEM CELLS, ADULT
Medical subject headings
Scleroderma, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLSBiological

Study groups in NCT02213705
Study groupRoleWhat they receive
INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLSExperimentalAdministration of allogeneic MSCs in the treatment of severe diffuse SSc or rapidly progressive and refractory to conventional treatments by prior cyclophosphamide
Receives: Biological: INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Immediate Toxicity

    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)

    Measured: 10 days

Secondary outcomes (11)

  1. Medium-term tolerance

    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.

    Measured: 2 years

  2. Survival

    Time from inclusion to death

    Measured: 2 years

  3. Progression free survival

    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

    Measured: 2 years

  4. CBC

    complete blood count (CBC)

    Measured: 1, 2, 3, 4, 8, 12, 16, 20, 24 weeks

  5. Platelet

    Platelet blood count

    Measured: 1, 2, 3, 4, 8, 12, 16, 20, 24 weeks

  6. Lymphocyte

    Lymphocyte subpopulation blood count measured by flow cytometry

    Measured: 3, 6, 9, 12, 15, 18, 24 months

  7. Antibody

    Antibody response

    Measured: 3, 6, 9, 12, 15, 18, 24 months

  8. Rodnan score

    modified Rodnan Score

    Measured: 3, 6, 9, 12, 15, 18, 24 months

  9. SHAQ

    Scleroderma Health Assessment Questionnaire (SHAQ)

    Measured: 3, 6, 9, 12, 15, 18, 24 months

  10. Clinical progression

    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,

    Measured: 3, 6, 9, 12, 15, 18, 24 months

  11. Clinical response

    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.

    Measured: 3, 6, 9, 12, 15, 18, 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2014 (estimated)
  2. Study start6 May 2014
  3. Primary completion9 Feb 2020
  4. Study completion16 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02213705
Sponsor's protocol ID
MSC Severe Systemic Sclerosis
Acronym
MSC
Status last verified
Oct 2020
First submitted
17 Jul 2014
Last updated
1 May 2024
Results posted
No

Publications

  • Farge D, Loisel S, Resche-Rigon M, Lansiaux P, Colmegna I, Langlais D, Charles C, Pugnet G, Maria ATJ, Chatelus E, Martin T, Hachulla E, Kheav VD, Lambert NC, Wang H, Michonneau D, Martinaud C, Sensebe L, Cras A, Tarte K. Safety and preliminary efficacy of allogeneic bone marrow-derived multipotent mesenchymal stromal cells for systemic sclerosis: a single-centre, open-label, dose-escalation, proof-of-concept, phase 1/2 study. Lancet Rheumatol. 2022 Feb;4(2):e91-e104. doi: 10.1016/S2665-9913(21)00326-X. Epub 2022 Jan 5.

    PubMed 38288741

  • Loisel S, Lansiaux P, Rossille D, Menard C, Dulong J, Monvoisin C, Bescher N, Bezier I, Latour M, Cras A, Farge D, Tarte K. Regulatory B Cells Contribute to the Clinical Response After Bone Marrow-Derived Mesenchymal Stromal Cell Infusion in Patients With Systemic Sclerosis. Stem Cells Transl Med. 2023 Apr 17;12(4):194-206. doi: 10.1093/stcltm/szad010.

    PubMed 36928395

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS in people with SYSTEMIC SCLERODERMA and ALLOGENEIC MESENCHYMAL STEM CELLS, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immediate Toxicity (time frame: 10 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02213705, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2024.

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