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Infusion of Allogeneic Mesenchymal Stem Cells in Patients With Diffuse Cutaneous Systemic Sclerosis With Refractory Pulmonary Involvement

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ClinicalTrials.gov Identifier: NCT04432545
Expanded Access Status : Available
First Posted : June 16, 2020
Last Update Posted : June 16, 2020
Fundación Neumologica Colombiana
Stem Medicina Regenerativa
CryoHoldco LATAM
Information provided by (Responsible Party):
Universidad de la Sabana

Brief Summary:

Progressive SSc is an entity with limited therapeutic alternatives and with asurvival rate of less than 45% in the first 3 to 5 years. The disease causessevere limitation in quality of life ranging from functional limitation to depression. Up to 20% of patients will be refractory to conventional treatment with diseasemodifying anti-rheumatic drugs (DMARDs) and cyclophosphamide therapy.This favors the progression to visceral involvement including gastrointestinal,lung and pulmonary hypertension. The latter being a poor prognostic factor,increases mortality in this group of patients and drastically affects their qualityof life. For this reason, different therapeutic options have been considered including cell transplantation and Stem Cell use. Among the options that have been studied so far are stromal mesenchymal cells from Wharton ́s jelly. These have been used in intravenous infusion or direct application in different disease scenarios ranging from vascular involvement to interstitial lung involvement and cases of pulmonary hypertension, with promising results in terms of clinical progression,improvement in quality of life and prognostic indices. This therapy has proven to have a significant margin of safety at the time of administration and a low rate of adverse events, a self-limiting fever as the most frequent event. Based on the above and considering the possibility of offering patients without therapeutic alternatives to their disease in addition to palliative options, an intravenous infusion of stromal mesenchymal stem cells from Wharton ́s jellyis proposed for three patients with progressive SSc refractory to conventional therapy with pulmonary involvement due to pulmonary hypertension.

Under this premise the question posed in our work is; What are the effects of the infusion of allogeneic mesenchymal stromal cells from Wharton ́s jellyin patients with systemic sclerosis refractory to conventional treatment with Methotrexate or Cyclophosphamide in a population of three patients with severe pulmonary involvement due to pulmonary hypertension.

Condition or disease Intervention/treatment
Systemic Sclerosis Pulmonary Pulmonary Hypertension Pulmonary Fibrosis Biological: Mesenchymal Stem Cells from Wharton ́s jellyintravenous infusion of Mesenchymal Stem Cells from Wharton ́s jelly

Detailed Description:

This study aims to evaluate the therapeutic effects of allogeneic mesenchymal stromal cell infusion as a treatment in patients with systemic sclerosis refractoryto conventional therapy. The group of patients will be collected from the database of families of Stem Regenerative Medicine according to the inclusion and exclusion criteria and verified in the academic committee.

The administration will be intravenously, with a concentration of 2 X 10^6 mesenchymal cells per kilogram of patient weight. The infusions will be carried out nested at cyclophosphamide application cycles ten days after each application of the cyclophosphamide schedule for each patient. To assess safety and therapeutic effects, the occurrence of any adverse event will be described from start of infusion until the conclusion of the trial in six months.

To assess the response, a pre-infusion and sixth-month post-infusion instrument will be applied that includes clinical variables, paraclinical and hemodynamic tests to evaluate skin involvement using the modified RODNAN score, changes in nail capillaroscopy, lung function and structural involvement by high-resolution chest tomography (hrCT), diffusion capacity for carbon monoxide (DLCO) and a 6-minute walk. As part of the cardiovascular assessment, cerebral natriuretic peptide (BNP), transthoracic echocardiogramwill be performed; The Cambridge Pulmonary Hypertension Outcome Review(CAMPHOR) and Sysq will be used as tools for the assessment of pulmonary hypertension. A comparison of these tests before initiation of therapy and after completion of 24 weeks of infusion scheme should be performed.

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Study Type : Expanded Access
Expanded Access Type : Intermediate-size Population
Official Title: Infusion of Allogeneic Stromal Mesenchymal Stem Cells From Wharton´s Jelly in Patients With Diffuse Cutaneous Systemic Sclerosis With Refractory Pulmonary Involvement to Treatment

Intervention Details:
  • Biological: Mesenchymal Stem Cells from Wharton ́s jellyintravenous infusion of Mesenchymal Stem Cells from Wharton ́s jelly
    Mesenchymal Stem Cells from Wharton ́s jellyintravenous infusion of Mesenchymal Stem Cells from Wharton ́s jelly

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age> 18 years and <65 years.• Established diagnosis of systemic sclerosis according to the criteria of theAmerican College of Rheumatology• SSc of poor prognosis, involving life-threatening severe visceralinvolvement (cardiac or pulmonary hypertension ), lack of response toconventional immunosuppressive therapy used in severe forms of thedisease according to the European recommendations of EUSTAR and EBMT, relying on high doses of IV cyclophosphamide (either in monthlybolus for at least six months); or SSc with life-threatening pulmonaryhypertension. Patients may or may not have pulmonary fibrosis.• Signed informed consent.• Presence of a consenting MSC donor• Affiliation to social security

Exclusion Criteria:

  • Pregnancy or absence of appropriate contraception throughout the study.• Pulmonary artery systolic pressure (PASP) >75mmHg (onechocardiography or after right heart catheterization);- Theorical DLCO <30%• Calculated creatinine clearance <30 ml/mn/m2• Clinical sign of a congestive heart failure refractory ;• Left ventricular ejection fraction <35% at myocardial scintigraphy orechocardiography;• Chronic atrial fibrillation requiring oral anticoagulant therapy;• Uncontrolled ventricular arrhythmia;• Pericardial effusion with hemodynamic compromise assessed byechocardiography.• Hepatic impairment defined as a persistent increase in transaminases orbilirubin 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 <200x 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, eosinophiliafasciitis.• 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): NCT04432545

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Contact: John Londono, MD,PhD +573187114885 john.londono@unisabana.edu.co
Contact: Mabel Avila, MD,PhD +573114747335 dircientifica@bancodecelulas.com

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Universidad de la Sabana Available
Chía, Chia, Colombia
Contact: John Londono, MD,PhD    573187114885    john.londono@unisabana.edu.co   
Contact: Mabel Avila, MD,PhD    573114747335    dircientifica@bancodecelulas.com   
Sponsors and Collaborators
Universidad de la Sabana
Fundación Neumologica Colombiana
Stem Medicina Regenerativa
CryoHoldco LATAM
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Principal Investigator: John Londono, MD,PhD Universidad de la Sabana

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Responsible Party: Universidad de la Sabana
ClinicalTrials.gov Identifier: NCT04432545    
Other Study ID Numbers: 2019-10
First Posted: June 16, 2020    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Keywords provided by Universidad de la Sabana:
Refractory systemic sclerosis
systemic sclerosis
pulmonary hypertension
mesenchymal stem cells
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Pulmonary Fibrosis
Scleroderma, Systemic
Scleroderma, Diffuse
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Connective Tissue Diseases
Skin Diseases