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

NCT04432545 | Unknown

• 1 other identifier: 2019-10
• Study Type: expanded_access
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Sclerosis Pulmonary; Pulmonary Hypertension; Pulmonary Fibrosis

Keywords

Refractory systemic sclerosis; systemic sclerosis; pulmonary hypertension; mesenchymal stem cells

Interventions

Mesenchymal Stem Cells from Wharton ́s jellyintravenous infusion of Mesenchymal Stem Cells from Wharton ́s jelly BIOLOGICAL

Mesenchymal Stem Cells from Wharton ́s jellyintravenous infusion of Mesenchymal Stem Cells from Wharton ́s jelly

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universidad de la Sabana: lead
• Fundación Neumologica Colombiana: collaborator
• Innocell SAS: collaborator
• Stem Medicina Regenerativa: collaborator

Study Sites (1)

Universidad de la Sabana

Chía, Chia, Colombia

AVAILABLE

Related Publications (4)

• Jaeger VK, Wirz EG, Allanore Y, Rossbach P, Riemekasten G, Hachulla E, Distler O, Airo P, Carreira PE, Balbir Gurman A, Tikly M, Vettori S, Damjanov N, Muller-Ladner U, Distler JH, Li M, Walker UA; EUSTAR co-authors. Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis: A Longitudinal EUSTAR Study. PLoS One. 2016 Oct 5;11(10):e0163894. doi: 10.1371/journal.pone.0163894. eCollection 2016.

  PMID: 27706206 BACKGROUND

• McNearney TA, Reveille JD, Fischbach M, Friedman AW, Lisse JR, Goel N, Tan FK, Zhou X, Ahn C, Feghali-Bostwick CA, Fritzler M, Arnett FC, Mayes MD. Pulmonary involvement in systemic sclerosis: associations with genetic, serologic, sociodemographic, and behavioral factors. Arthritis Rheum. 2007 Mar 15;57(2):318-26. doi: 10.1002/art.22532.

  PMID: 17330281 BACKGROUND

• Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B, Mayes MD, Nash RA, Crofford LJ, Eggleston B, Castina S, Griffith LM, Goldstein JS, Wallace D, Craciunescu O, Khanna D, Folz RJ, Goldin J, St Clair EW, Seibold JR, Phillips K, Mineishi S, Simms RW, Ballen K, Wener MH, Georges GE, Heimfeld S, Hosing C, Forman S, Kafaja S, Silver RM, Griffing L, Storek J, LeClercq S, Brasington R, Csuka ME, Bredeson C, Keever-Taylor C, Domsic RT, Kahaleh MB, Medsger T, Furst DE; SCOT Study Investigators. Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma. N Engl J Med. 2018 Jan 4;378(1):35-47. doi: 10.1056/nejmoa1703327.

  PMID: 29298160 BACKGROUND

• van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, Schuerwegh AJ, Marijt EW, Vonk MC, Schattenberg AV, Matucci-Cerinic M, Voskuyl AE, van de Loosdrecht AA, Daikeler T, Kotter I, Schmalzing M, Martin T, Lioure B, Weiner SM, Kreuter A, Deligny C, Durand JM, Emery P, Machold KP, Sarrot-Reynauld F, Warnatz K, Adoue DF, Constans J, Tony HP, Del Papa N, Fassas A, Himsel A, Launay D, Lo Monaco A, Philippe P, Quere I, Rich E, Westhovens R, Griffiths B, Saccardi R, van den Hoogen FH, Fibbe WE, Socie G, Gratwohl A, Tyndall A; EBMT/EULAR Scleroderma Study Group. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014 Jun 25;311(24):2490-8. doi: 10.1001/jama.2014.6368.

  PMID: 25058083 BACKGROUND

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Fibrosis; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• John Londono, MD,PhD

  Universidad de la Sabana

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Londono, MD,PhD

CONTACT

+573187114885; john.londono@unisabana.edu.co

Mabel Avila, PhD

CONTACT

+573114747335; dircientifica@bancodecelulas.com

Study Design

• Study Type: expanded access
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2020
• First Posted: June 16, 2020
• Last Updated: April 8, 2024

Record last verified: 2024-04

Locations

CO (1)