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

NCT02213705 | Completed Phase 1

• 1 other identifier: MSC Severe Systemic Sclerosis
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

SYSTEMIC SCLERODERMA; ALLOGENEIC MESENCHYMAL STEM CELLS; ADULT

Keywords

SYSTEMIC SCLERODERMA; TRANSPLANTATION; ALLOGENEIC MESENCHYMAL STEM CELLS; ADULT

Outcome Measures

Primary Outcomes (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)

  10 days

Secondary Outcomes (11)

• Medium-term tolerance

  2 years

• Survival

  2 years

• Progression free survival

  2 years

• CBC

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

• Platelet

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

Study Arms (1)

INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS

EXPERIMENTAL

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

Interventions

INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS BIOLOGICAL

INJECTION OF ALLOGENEIC MESENCHYMAL STEM CELLS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 :
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Saint-Louis Hospital

Paris, 75010, France

Location

Related Publications (2)

• 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.

  PMID: 38288741 BACKGROUND

• 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.

  PMID: 36928395 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• dominique farges, MDPHD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2014
• First Posted: August 11, 2014
• Study Start: May 6, 2014
• Primary Completion: February 9, 2020
• Study Completion: June 16, 2022
• Last Updated: May 1, 2024

Record last verified: 2020-10

Locations

FR (1)