Graft vs Host DiseasePhase 1MSC-GvHDNCT01764100
Mesenchymal Stromal Cells (MSCs) for the Treatment of Graft Versus Host Disease (GVHD)
A Phase 1 study testing Mesenchymal stromal cells in people with Graft vs Host Disease, run by Ettore Biagi, MD at 3 sites in Italy.
Trial summary
This is a bicentric, prospective, non randomized study. Pediatric and adult patients will be treated. Rationale: MSC have shown promising effects by reversal of severe therapy-resistant acute GvHD. 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 stromal cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 3 sitesItaly
- Study dates
- Sep 2009to Sep 2013
- Phase
- Phase 1
- 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
- Informed consent.
- Patients are required to meet the following inclusion criteria:
- Any patient that has undergone allogeneic stem cell transplantation with steroid refractory grades II-IV acute GvHD either occurring post transplant, or induced by donor lymphocyte infusions (DLI) or T-cell add back, or chronic steroid refractory GVHD in acute phase. Patients may be receiving local best treatment for steroid refractory GVHD. A positive biopsy for GvHD is not required if clinical signs and symptoms are characteristic for GvHD and other etiologies are excluded. See 6.4 for acute GvHD grading.
- Steroids have been given, for instance methylprednisolone 2 mg/kg/day, for at least 72h in case of progressive acute GvHD, 5 days in case of stable acute GVHD (grade II to IV) or chronic GvHD in active phase, according to the local policy.
- Despite this treatment, the patient has unresponsive GvHD after 5 days, or progressive acute GvHD after 72 hours. If single organ acute GvHD grade II from gut or liver, either progression from single organ or addition of one or two more organs. As an example, if the patient has grade II acute GvHD of the skin, GvHD is more intense and more widespread, or GvHD also includes liver and/or gut.
- Patients with steroid refractory GvHD fulfilling the requirements mentioned in a) - b) may be treated with second line therapy according to the clinical guidelines at each center prior to enrolment in this study.
- Patients under treatment with best available local treatment for steroid resistant GVHD will not interrupt the ongoing treatment unless clinically required for safety reasons.
Who cannot join
- Inability to obtain informed consent.
- Patients with documented uncontrolled EBV, CMV or fungal infection.
- Patients in poor clinical conditions with life expectancy of less than 30 days.
Trial locations and contacts
3 sites in 1 country.
Italy3 sites, 3 recruiting
- Recruiting
U.O. Ematologia - Ospedali Riuniti di Bergamo
Bergamo, BG, 24128
Alessandro Rambaldi, MD, arambaldi@ospedaliriuniti.bergamo.it
Alessandro Rambaldi, MD
- Recruiting
Clinica Pediatrica CTMO - Azienda Ospedaliera San Gerardo
Monza, MB, 20052
Ettore Biagi, MD, e.biagi@hsgerardo.org
Ettore Biagi, MD
- Recruiting
U.O. Ematologia CTMO - Azienda Ospedaliera San Gerardo
Monza, MB, 20052
Matteo Parma, MD, m.parma@hsgerardo.org
Matteo Parma, MD
About this study
Official title: Mesenchymal Stromal Cells (MSC) for the Treatment of Severe (Grade II-IV) Steroid-resistant Graft Versus Host Disease (GVHD): a Phase I Trial
This is a bicentric, prospective, non randomized study. Pediatric and adult patients will be treated.
Rationale: MSC have shown promising effects by reversal of severe therapy-resistant acute GvHD. As a common therapeutic line of action is not shared for steroid resistant GVHD, it is important to establish the toxicity and the feasibility of preparation and infusion of third party MSCs for acute steroid resistant GVHD and acute phases of chronic steroid resistant GVHD.
Read more
A total of 10 patients (pediatric and adults) need to be enrolled in the study. Patients who present clinical signs of either acute or chronic steroid resistant GVHD will receive by intravenous infusion at least two fixed doses of mesenchymal stem cells with 5 to 7 days of interval one from the other, derived from HLA unrelated donor different from the HSC donor (third party donor) regardless of the rate of HLA mismatch.
Primary objectives are to establish the feasibility and the toxicity of preparation and infusions of third party MSCs for the treatment of steroid resistant acute and acute phases of chronic grade II-IV GVHD.
Secondary objectives are:
- To document the efficacy of MSC infusion in steroid resistant acute and acute phases of chronic GVHD grade II-IV.
- To document the rate of GVHD recurrence in MSCs infused patients.
- To document relapse of hematological malignancies post MSC infusions in patients undergoing MSCs treatment for steroid refractory GvHD.
- To document the overall survival of MSC infused patients for steroid refractory GvHD.
- Conditions
- Graft vs Host Disease
- Being tested
- Mesenchymal stromal cells
- 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 stromal cellsGenetic
Mesenchymal stromal cells (MSC) intravenous infusion at least two fixed doses of mesenchymal stem cells (1 ± 0.5 x 106/kg recipient body weight for each injection) with 5 to 7 days of interval one from the other, derived from HLA unrelated donor different from the HSC donor (third party donor).
| Study group | Role | What they receive |
|---|---|---|
| Mesenchymal Stromal Cells (MSC) | Experimental | Intravenous injections for a dose of 1 ± 0.5 x 106 MSC/kg recipient body weight Receives: Genetic: Mesenchymal stromal cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Any toxic effect reported during MSCs infusion or in the subsequent 10 days by clinical monitoring
Measured: During MSCs infusion or in the subsequent 10 days
Feasibility as the possibility of producing adequate lots of patient dedicated MSCs for any patients presenting with steroid resistant GVHD
Measured: three years
Secondary outcomes (4)
Number of patients with GvHD resolution
- Complete resolution of GvHD: Control of all signs and symptoms attributed to acute GvHD
- Partial resolution of GvHD: Control of some signs and symptoms attributed to acute GvHD with an improvement of overall grade
- Refractory GvHD: No change in signs or symptoms of GvHD within 10 days of MSC infusion.
- Worsening GvHD: Any progress of GvHD signs and symptoms that increase overall grade. a and b will be defined as response. c and d will be defined as no response.
Measured: One month
Determination of recurrence of GvHD
Measured: After 1 month from MSCs infusion
Relapse of haematological disease
Measured: Every three months
Survival
Measured: Every three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2013 (estimated)
- Study startSep 2009
- Primary completionMay 2013 (estimated)
- Study completionSep 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ettore Biagi, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ettore Biagi, MD, Azienda Ospedaliera San Gerardo di Monza
- Investigators
- Ettore Biagi, MD, Principal investigator, San Gerardo Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01764100
- Sponsor's protocol ID
- PTC-MSC
- Other IDs
- 2008-007869-23, 2008
- Acronym
- MSC-GvHD
- Status last verified
- Jan 2013
- First submitted
- 5 May 2010
- Last updated
- 9 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Introna M, Lucchini G, Dander E, Galimberti S, Rovelli A, Balduzzi A, Longoni D, Pavan F, Masciocchi F, Algarotti A, Mico C, Grassi A, Deola S, Cavattoni I, Gaipa G, Belotti D, Perseghin P, Parma M, Pogliani E, Golay J, Pedrini O, Capelli C, Cortelazzo S, D'Amico G, Biondi A, Rambaldi A, Biagi E. Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients. Biol Blood Marrow Transplant. 2014 Mar;20(3):375-81. doi: 10.1016/j.bbmt.2013.11.033. Epub 2013 Dec 7.
PubMed 24321746
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mesenchymal Stromal Cells (MSC) for the Treatment of Severe (Grade II-IV) Steroid-resistant Graft Versus Host Disease (GVHD): a Phase I Trial
- ClinicalTrials.gov ID
- NCT01764100
- Acronym / sponsor ID
- MSC-GvHD / PTC-MSC
- Conditions
- Graft vs Host Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Ettore Biagi, MDUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- May 2013 (estimated)
- Study completion
- Sep 2013 (estimated)
- First posted
- 9 Jan 2013 (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.
This is a bicentric, prospective, non randomized study. Pediatric and adult patients will be treated.
Rationale: MSC have shown promising effects by reversal of severe therapy-resistant acute GvHD. As a common therapeutic line of action is not shared for steroid resistant GVHD, it is important to establish the toxicity and the feasibility of preparation and infusion of third party MSCs for acute steroid resistant GVHD and acute phases of chronic steroid resistant GVHD.
A total of 10 patients (pediatric and adults) need to be enrolled in the study. Patients who present clinical signs of either acute or chronic steroid resistant GVHD will receive by intravenous infusion at least two fixed doses of mesenchymal stem cells with 5 to 7 days of interval one from the other, derived from HLA unrelated donor different from the HSC donor (third party donor) regardless of the rate of HLA mismatch.
Primary objectives are to establish the feasibility and the toxicity of preparation and infusions of third party MSCs for the treatment of steroid resistant acute and acute phases of chronic grade II-IV GVHD.
Secondary objectives are:
- To document the efficacy of MSC infusion in steroid resistant acute and acute phases of chronic GVHD grade II-IV.
- To document the rate of GVHD recurrence in MSCs infused patients.
- To document relapse of hematological malignancies post MSC infusions in patients undergoing MSCs treatment for steroid refractory GvHD.
- To document the overall survival of MSC infused patients for steroid refractory GvHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal Stromal Cells (MSC) | Experimental | Genetic: Mesenchymal stromal cellsIntravenous injections for a dose of 1 ± 0.5 x 106 MSC/kg recipient body weight |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Informed consent.
- Patients are required to meet the following inclusion criteria:
- Any patient that has undergone allogeneic stem cell transplantation with steroid refractory grades II-IV acute GvHD either occurring post transplant, or induced by donor lymphocyte infusions (DLI) or T-cell add back, or chronic steroid refractory GVHD in acute phase. Patients may be receiving local best treatment for steroid refractory GVHD. A positive biopsy for GvHD is not required if clinical signs and symptoms are characteristic for GvHD and other etiologies are excluded. See 6.4 for acute GvHD grading.
- Steroids have been given, for instance methylprednisolone 2 mg/kg/day, for at least 72h in case of progressive acute GvHD, 5 days in case of stable acute GVHD (grade II to IV) or chronic GvHD in active phase, according to the local policy.
- Despite this treatment, the patient has unresponsive GvHD after 5 days, or progressive acute GvHD after 72 hours. If single organ acute GvHD grade II from gut or liver, either progression from single organ or addition of one or two more organs. As an example, if the patient has grade II acute GvHD of the skin, GvHD is more intense and more widespread, or GvHD also includes liver and/or gut.
Key exclusion criteria (3 listed)
- Inability to obtain informed consent.
- Patients with documented uncontrolled EBV, CMV or fungal infection.
- Patients in poor clinical conditions with life expectancy of less than 30 days.
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 stromal cellsMesenchymal stromal cells (MSC) intravenous infusion at least two fixed doses of mesenchymal stem cells (1 ± 0.5 x 106/kg recipient body weight for each injection) with 5 to 7 days of interval one from the other, derived from HLA unrelated donor different from the HSC donor (third party donor). | Genetic | Mesenchymal Stromal Cells (MSC) |
Primary outcome
Any toxic effect reported during MSCs infusion or in the subsequent 10 days by clinical monitoring
Time frame: During MSCs infusion or in the subsequent 10 days
Feasibility as the possibility of producing adequate lots of patient dedicated MSCs for any patients presenting with steroid resistant GVHD
Time frame: three years
4 secondary outcomes
Number of patients with GvHD resolution
Time frame: One month
Determination of recurrence of GvHD
Time frame: After 1 month from MSCs infusion
Relapse of haematological disease
Time frame: Every three months
Survival
Time frame: Every three months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2013.
- Derived from this study: PubMed 24321746Introna M, Lucchini G, Dander E, Galimberti S, Rovelli A, Balduzzi A, Longoni D, Pavan F, Masciocchi F, Algarotti A, Mico C, Grassi A, Deola S, Cavattoni I, Gaipa G, Belotti D, Perseghin P, Parma M, Pogliani E, Golay J, Pedrini O, Capelli C, Cortelazzo S, D'Amico G, Biondi A, Rambaldi A, Biagi E. Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients. Biol Blood Marrow Transplant. 2014 Mar;20(3):375-81. doi: 10.1016/j.bbmt.2013.11.033. Epub 2013 Dec 7.
Related trials for Graft vs Host Disease
Active, not recruitingPhase 2
De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis
Graft-versus-host Disease
RecruitingEarly Phase 1
HMCT/CT2401: Abatacept GVHD Prophylaxis Following Omidubicel HCT
Hematologic Malignancy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
RecruitingPhase 1/2
The Lowest Effective Dose of Post-Transplantation Cyclophosphamide in Combination With Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis After Reduced Intensity Conditioning and Peripheral Blood Stem Cell Transplantation
Peripheral Blood Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation
RecruitingPhase 1/2
Phase I/II Study of Pacritinib, A JAK2/IRAK1/CSF1R Inhibitor, in Refractory Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
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.
Ettore Biagi, MD principal investigator
San Gerardo Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mesenchymal stromal cells in people with Graft vs Host Disease, run by Ettore Biagi, MD at 3 sites in Italy.
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 7 inclusion and 3 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 9 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Ettore Biagi, MD (+39 039 233 ext. 2232, e.biagi@hsgerardo.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Any toxic effect reported during MSCs infusion or in the subsequent 10 days by clinical monitoring (time frame: During MSCs infusion or in the subsequent 10 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01764100, which also lists 1 linked publication.
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 9 Jan 2013.