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

NCT ID: NCT01764100

Last Updated: 2013-01-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2013-09-30

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:

1. To document the efficacy of MSC infusion in steroid resistant acute and acute phases of chronic GVHD grade II-IV.

2. To document the rate of GVHD recurrence in MSCs infused patients.

3. To document relapse of hematological malignancies post MSC infusions in patients undergoing MSCs treatment for steroid refractory GvHD.

4. To document the overall survival of MSC infused patients for steroid refractory GvHD.

Conditions

Graft vs Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mesenchymal Stromal Cells (MSC)

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

Group Type: EXPERIMENTAL

Mesenchymal stromal cells

Intervention Type: GENETIC

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).

Interventions

Mesenchymal stromal cells

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).

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

1. Informed consent.

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.

1. 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.

2. 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.

3. 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.

4. 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

1. Inability to obtain informed consent.

2. Patients with documented uncontrolled EBV, CMV or fungal infection.

3. Patients in poor clinical conditions with life expectancy of less than 30 days.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ettore Biagi, MD

OTHER

Sponsor Role: lead

Responsible Party

Ettore Biagi, MD

Ettore Biagi, MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ettore Biagi, MD

Role: PRINCIPAL_INVESTIGATOR

San Gerardo Hospital

Locations

U.O. Ematologia - Ospedali Riuniti di Bergamo

Bergamo, BG, Italy

Site Status: RECRUITING

Clinica Pediatrica CTMO - Azienda Ospedaliera San Gerardo

Monza, MB, Italy

Site Status: RECRUITING

U.O. Ematologia CTMO - Azienda Ospedaliera San Gerardo

Monza, MB, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Ettore Biagi, MD

Role: CONTACT

e.biagi@hsgerardo.org

+39 039 233 ext. 2232

Facility Contacts

Alessandro Rambaldi, MD

Role: primary

arambaldi@ospedaliriuniti.bergamo.it

Ettore Biagi, MD

Role: primary

e.biagi@hsgerardo.org

Matteo Parma, MD

Role: primary

m.parma@hsgerardo.org

References

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.

Reference Type: DERIVED

PMID: 24321746 (View on PubMed)

Other Identifiers

2008-007869-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PTC-MSC

Identifier Type: -

Identifier Source: org_study_id