- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT02770430
Mesenchymal Stem Cells as First Treatment Line for Resistant Acute Graft Versus Host Disease
A Phase II, Randomized Study to Evaluate the Human Mesenchymal Stem Cells as a First-line Treatment for aGVHD in Patients Steroids Resistant.
Steroids are still the first line treatment for established severe acute-graft-versus-host-disease (aGVHD), with a response rate of 30-50%, and there is no established and effective therapy for severe steroid-refractory (aGVHD). The outcome for patients is poor and overall survival low, with few patients alive at 2 years.
In the case of failure after corticosteroid treatment, different therapeutic options have been introduced as second or third-line strategies. In this scenario, infusion of ex vivo expanded mesenchymal stromal cells (MSCs) has emerged as an additional tool for treatment of GVHD.
The purpose of this work is conduct a study in patients with refractory and/or resistant GVHD corticosteroids treatment. It will be randomized into two groups: one group that will receive the MSCs and the other group will follow the acute GVHD steroid-resistant and/or refractory treatment according to the routines of the Bone Marrow Transplantation (BMT) service of Hospital de Clinicas de Porto Alegre. It will be evaluated aspects of immune recovery early after MSCs infusion.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
Allogeneic hematopoietic stem cell transplant (AlloSCT) is the treatment of choice for many malignant and non-malignant hematological disorders. However, this treatment is frequently complicated by acute graft-versus-host-disease (aGVHD), wich can be associated with high morbidity and mortality.
Steroids are still the first line treatment for established aGVHD, with a response rate of 30-50%, and there is no established and effective therapy for severe steroid-refractory aGVHD. The outcome for patients is poor and overall survival low, with few patients alive at 2 years.
In the case of failure after corticosteroid treatment, different therapeutic options have been introduced as second or third-line strategies. In this scenario, infusion of ex vivo expanded mesenchymal stem cells (MSCs) has emerged as an additional tool for treatment of GVHD.
MSCs are non hematopoietic multipotent cells with self-renewal properties and the ability to differentiate into mesenchymal tissues. Several lines of evidence in the past few years have confirmed the ability of theses cells differentiate into cells derived form embryonic mesoderm, such as osteocytes, adipocytes and chondroblasts. In vitro, culture-expanded MSCs express membrane antigens that can be immunophenotyped by flow cytometry. The most widely accepted antigen expression pattern is cluster of differentiation (CD) 29, CD105, CD73, and CD90 positivity in 97 % of cells and minimal expression of CD45, CD34, CD3, CD14, CD19, or human leukocyte antigen (HLA) -DR, which should be positive in less than 3 % of cells.
Because they are easy to isolate and culture and due to their differentiation potential and production of growth factors and cytokines, MSC have become ideal candidates for regenerative protocols.
The purpose of this work is conduct a study in patients with refractory and/or resistant GVHD corticosteroids treatment. It will be randomized into two groups: one group that will receive the MSCs and the other group will follow the acute GVHD steroid-resistant and/or refractory treatment according to the routines of the Bone Marrow Transplantation service of Hospital de Clinicas de Porto Alegre. It will be evaluated aspects of immune recovery early after MSCs infusion.
METHOD: This is a prospective, randomized, controlled, open label study to evaluate the effectiveness of early treatment of steroid-resistant acute GVHD with MSC. All patients with refractory and/or resistant steroids GVHD will be included after signing of free and informed consent.
After randomization, patients will be allocated to receive conventional treatment:
- Basiliximab 20mg dose for adults and 10mg for children, 1 time a week or every 3 days if worsens the stage of GVHD until reaching Very Good Partial Response (VGPR) or for a maximum of 4 doses, whichever comes first.
- If after the item (1) will not obtained VGPR: Infliximab 5 to 10 mg/kg dose, 1 time a week, four weeks or even VGPR.
Patients in the study group will receive two infusions of MSC per week during two weeks and 1 more MSC infusion (2 + 2 + 1 scheme).
After 28 days, if VGPR is not obtained, crossover between groups will be allowed as well as for the patients with progressive GVHD in spit of treatment arm, before day +28. The latter group of patients, who use both treatments (MSC + Conventional treatment) before day + 28 will be analyzed separately.
Bone marrow (BM) derived MSCs from normal BMT donors (third part) will be isolated and expanded under conditions of Good Manufacturing Practice. The quality control involves immunophenotyping, differentiation, microbiological control, mycoplasma and endotoxin tests.
Patients response evaluation will be at Day + 28:
- Complete response: disappearance of all symptoms
- Partial response: with a decrease at least of one degree of GVHD
- VGPR: decrease to the stage I of GVHD
- Stable disease: when there is a stability of the disease
- Number and type of infection in the first 100 days after transplant
The transplant-related mortality, disease-free survival, overall survival and the development of chronic GVHD or not, will also be evaluated.
Studientyp
Einschreibung (Voraussichtlich)
Phase
- Phase 2
Kontakte und Standorte
Studienorte
-
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Rio Grande do Sul
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Porto Alegre, Rio Grande do Sul, Brasilien, 90035-903
- Rekrutierung
- Centro Terapia e Tecnologia Celular
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Kontakt:
- Lucia Silla, PhD
- Telefonnummer: 55 51 33597516
- E-Mail: dralucia.silla@gmail.com
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Kontakt:
- Vanessa Valim, Msc
- Telefonnummer: 55 51 33598850
- E-Mail: vanessavalim@gmail.com
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-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Kind
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
- All patients with refractory and/or resistant steroids GVHD will be included after signing of free and informed consent.
Exclusion Criteria:
- They will be excluded from the study, patients who did not agree to participate and don't sign an informed consent (which is going to receive conventional treatment) and that patients who is a Grade I refractory GVHD.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Crossover-Aufgabe
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Aktiver Komparator: conventional treatment
After randomization, patients will be allocated to receive conventional treatment:
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Andere Namen:
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Experimental: mesenchymal stem cells
Patients in the study group will receive two infusions of MSC per week during two weeks and 1 more MSC infusion (2 + 2 + 1 scheme).
Dosage: 2x10E6/Kg
|
MSCs derived from bone marrow (BM) will be isolated and expanded in the laboratory under conditions of Good Manufacturing Practice.
The quality control involves immunophenotyping, differentiation, microbiological control, mycoplasma and endotoxin tests.
Patients will receive five infusions of MSC.
Dosage: 2x10E6 cells/Kg
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Complete response: disappearance of all symptoms
Zeitfenster: It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
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It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Partial response: with a decrease at least of one degree of GVHD
Zeitfenster: It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
|
It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
|
VGPR: decrease to the stage I of GVHD
Zeitfenster: It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
|
It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
|
Stable disease: when there is a stability of the disease (by Clinical evaluation)
Zeitfenster: It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
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It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
|
Number of infection (by Clinical and laboratory evaluation)
Zeitfenster: First 100 days after transplant
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First 100 days after transplant
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Type of infection (by Clinical and laboratory evaluation)
Zeitfenster: First 100 days after transplant
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First 100 days after transplant
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Mitarbeiter und Ermittler
Ermittler
- Hauptermittler: Lucia S Silla, Hospital de Clinicas de Porto Alegre
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Voraussichtlich)
Studienabschluss (Voraussichtlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 12-0407
Plan für individuelle Teilnehmerdaten (IPD)
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