Graft vs Host DiseasePhase 2NCT02770430
Mesenchymal Stem Cells as First Treatment Line for Resistant Acute Graft Versus Host Disease
A Phase 2 study testing mesenchymal stem cells and conventional treatment in people with Graft vs Host Disease, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
Trial 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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Graft vs Host Disease
- What is being tested?
- mesenchymal stem cells and conventional treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteBrazil
- Study dates
- Sep 2015to Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients with refractory and/or resistant steroids GVHD will be included after signing of free and informed consent.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Centro Terapia e Tecnologia Celular
Porto Alegre, Rio Grande do Sul, 90035-903
Lucia Silla, PhD, 55 51 33597516, dralucia.silla@gmail.com
Vanessa Valim, Msc, 55 51 33598850, vanessavalim@gmail.com
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Graft vs Host Disease
- Being tested
- mesenchymal stem cells, conventional treatment
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mesenchymal stem cellsBiological
Also called mesenchymal stomal cells
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
conventional treatmentDrug
Also called Basiliximab and/or Infliximab
- 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.
| Study group | Role | What they receive |
|---|---|---|
| conventional treatment | Active comparator | After 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. Receives: Drug: conventional treatment |
| mesenchymal stem cells | Experimental | 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 Receives: Biological: mesenchymal stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response: disappearance of all symptoms
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: First 100 days after transplant
Type of infection (by Clinical and laboratory evaluation)
Measured: First 100 days after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2016 (estimated)
- Study startSep 2015
- Primary completionSep 2017 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lucia S Silla, Principal investigator, Hospital de Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02770430
- Sponsor's protocol ID
- 12-0407
- Status last verified
- May 2016
- First submitted
- 8 Oct 2015
- Last updated
- 12 May 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized Study to Evaluate the Human Mesenchymal Stem Cells as a First-line Treatment for aGVHD in Patients Steroids Resistant.
- ClinicalTrials.gov ID
- NCT02770430
- Acronym / sponsor ID
- 12-0407
- Conditions
- Graft vs Host Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Sep 2017 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 12 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| conventional treatment | Active comparator | Drug: conventional treatmentAfter 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 | Experimental | Biological: mesenchymal stem cellsPatients 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All patients with refractory and/or resistant steroids GVHD will be included after signing of free and informed consent.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mesenchymal stem cellsAlso: mesenchymal stomal cellsMSCs 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 | Biological | mesenchymal stem cells |
| conventional treatmentAlso: Basiliximab and/or Infliximab1. 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. | Drug | conventional treatment |
Primary outcome
Complete response: disappearance of all symptoms
Time frame: It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.
5 secondary outcomes
Partial response: with a decrease at least of one degree of GVHD
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: First 100 days after transplant
Type of infection (by Clinical and laboratory evaluation)
Time frame: First 100 days after transplant
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2016.
- Individual participant dataSharing planned: Undecided
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Graft vs Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lucia S Silla principal investigator
Hospital de Clinicas de Porto Alegre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing mesenchymal stem cells and conventional treatment in people with Graft vs Host Disease, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lucia Silla, PhD (55 51 33597516, dralucia.silla@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response: disappearance of all symptoms (time frame: It will be evaluated the patients response who received MSC infusion or conventional therapy in the 28th day of the study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2016.