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.
1 other identifier
interventional
90
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2015
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2015
CompletedFirst Submitted
Initial submission to the registry
October 8, 2015
CompletedFirst Posted
Study publicly available on registry
May 12, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2018
CompletedMay 12, 2016
May 1, 2016
2 years
October 8, 2015
May 10, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Complete response: disappearance of all symptoms
It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
Secondary Outcomes (5)
Partial response: with a decrease at least of one degree of GVHD
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
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)
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)
First 100 days after transplant
Type of infection (by Clinical and laboratory evaluation)
First 100 days after transplant
Study Arms (2)
conventional treatment
ACTIVE COMPARATORAfter randomization, patients will be allocated to receive conventional treatment: 1. 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. 2. 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.
mesenchymal stem cells
EXPERIMENTALPatients 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
Interventions
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
1. 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. 2. 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.
Eligibility Criteria
You may qualify if:
- All patients with refractory and/or resistant steroids GVHD will be included after signing of free and informed consent.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Centro Terapia e Tecnologia Celular
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lucia S Silla
Hospital de Clínicas de Porto Alegre
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 8, 2015
First Posted
May 12, 2016
Study Start
September 1, 2015
Primary Completion
September 1, 2017
Study Completion
December 1, 2018
Last Updated
May 12, 2016
Record last verified: 2016-05