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

NCT01764100 | Unknown Phase 1

• 2 other identifiers: PTC-MSC2008-007869-23
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

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. 1.To document the efficacy of MSC infusion in steroid resistant acute and acute phases of chronic GVHD grade II-IV.
2. 2.To document the rate of GVHD recurrence in MSCs infused patients.
3. 3.To document relapse of hematological malignancies post MSC infusions in patients undergoing MSCs treatment for steroid refractory GvHD.
4. 4.To document the overall survival of MSC infused patients for steroid refractory GvHD.

Conditions

Graft vs Host Disease

Outcome Measures

Primary Outcomes (2)

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

  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

  three years

Secondary Outcomes (4)

• Number of patients with GvHD resolution

  One month

• Determination of recurrence of GvHD

  After 1 month from MSCs infusion

• Relapse of haematological disease

  Every three months

• Survival

  Every three months

Study Arms (1)

Mesenchymal Stromal Cells (MSC)

EXPERIMENTAL

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

Genetic: Mesenchymal stromal cells

Interventions

Mesenchymal stromal cells 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).

Mesenchymal Stromal Cells (MSC)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ettore Biagi, MD: lead

Study Sites (3)

U.O. Ematologia - Ospedali Riuniti di Bergamo

Bergamo, BG, 24128, Italy

RECRUITING

Clinica Pediatrica CTMO - Azienda Ospedaliera San Gerardo

Monza, MB, 20052, Italy

RECRUITING

U.O. Ematologia CTMO - Azienda Ospedaliera San Gerardo

Monza, MB, 20052, Italy

RECRUITING

Related Publications (1)

• 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.

  PMID: 24321746 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Ettore Biagi, MD

  San Gerardo Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ettore Biagi, MD

CONTACT

+39 039 233; e.biagi@hsgerardo.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Ettore Biagi, MD

Study Record Dates

• First Submitted: May 5, 2010
• First Posted: January 9, 2013
• Study Start: September 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: September 1, 2013
• Last Updated: January 9, 2013

Record last verified: 2013-01

Locations

IT (3)