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Mesenchymal Stromal Cells (MSCs) for the Treatment of Graft Versus Host Disease (GVHD) (MSC-GvHD)

Primary Purpose

Graft vs Host Disease

Status

Unknown status

Phase

Phase 1

Locations

Italy

Study Type

Interventional

Intervention

Mesenchymal stromal cells

About this trial

This is an interventional treatment trial for Graft vs Host Disease

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

U.O. Ematologia - Ospedali Riuniti di BergamoRecruiting
Clinica Pediatrica CTMO - Azienda Ospedaliera San GerardoRecruiting
U.O. Ematologia CTMO - Azienda Ospedaliera San GerardoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mesenchymal Stromal Cells (MSC)

Arm Description

Intravenous injections for a dose of 1 ± 0.5 x 106 MSC/kg recipient body weight

Outcomes

Primary Outcome Measures

Any toxic effect reported during MSCs infusion or in the subsequent 10 days by clinical monitoring

Feasibility as the possibility of producing adequate lots of patient dedicated MSCs for any patients presenting with steroid resistant GVHD

Secondary Outcome Measures

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.

Determination of recurrence of GvHD

Relapse of haematological disease

Survival

Full Information

NCT ID

NCT01764100

First Posted

May 5, 2010

Last Updated

January 7, 2013

Sponsor

Ettore Biagi, MD

1. Study Identification

Unique Protocol Identification Number

NCT01764100

Brief Title

Mesenchymal Stromal Cells (MSCs) for the Treatment of Graft Versus Host Disease (GVHD)

Acronym

MSC-GvHD

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Unknown status

Study Start Date

September 2009 (undefined)

Primary Completion Date

May 2013 (Anticipated)

Study Completion Date

September 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Ettore Biagi, MD

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft vs Host Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Mesenchymal Stromal Cells (MSC)

Arm Type

Experimental

Arm Description

Intravenous injections for a dose of 1 ± 0.5 x 106 MSC/kg recipient body weight

Intervention Type

Genetic

Intervention Name(s)

Mesenchymal stromal cells

Intervention Description

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).

Primary Outcome Measure Information:

Title

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

Title

Feasibility as the possibility of producing adequate lots of patient dedicated MSCs for any patients presenting with steroid resistant GVHD

Time Frame

three years

Secondary Outcome Measure Information:

Title

Number of patients with GvHD resolution

Description

Time Frame

One month

Title

Determination of recurrence of GvHD

Time Frame

After 1 month from MSCs infusion

Title

Relapse of haematological disease

Time Frame

Every three months

Title

Survival

Time Frame

Every three months

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ettore Biagi, MD

Phone

+39 039 233

Ext

2232

e.biagi@hsgerardo.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ettore Biagi, MD

Organizational Affiliation

San Gerardo Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

U.O. Ematologia - Ospedali Riuniti di Bergamo

City

Bergamo

State/Province

ZIP/Postal Code

24128

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alessandro Rambaldi, MD

arambaldi@ospedaliriuniti.bergamo.it

First Name & Middle Initial & Last Name & Degree

Alessandro Rambaldi, MD

Facility Name

Clinica Pediatrica CTMO - Azienda Ospedaliera San Gerardo

City

Monza

State/Province

ZIP/Postal Code

20052

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ettore Biagi, MD

e.biagi@hsgerardo.org

First Name & Middle Initial & Last Name & Degree

Ettore Biagi, MD

Facility Name

U.O. Ematologia CTMO - Azienda Ospedaliera San Gerardo

City

Monza

State/Province

ZIP/Postal Code

20052

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Matteo Parma, MD

m.parma@hsgerardo.org

First Name & Middle Initial & Last Name & Degree

Matteo Parma, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

24321746

Citation

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.

Results Reference

derived

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Mesenchymal Stromal Cells (MSCs) for the Treatment of Graft Versus Host Disease (GVHD)

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