Umbilical Cord Derived Mesenchymal Stromal Cells For The Treatment of Severe Steroid-resistant Graft Versus Host Disease

Hematologic Malignancies Clinical Trial

— PTC-UC-MSC  

Official title:

UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC) FOR THE TREATMENT OF SEVERE (GRADE III-IV) STEROID-RESISTANT GRAFT VERSUS HOST DISEASE (GvHD): A PHASE I/II TRIAL

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02032446
• Other study ID #: EudraCT 2012-000582-21
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 2013
• Est. completion date: September 2019

Study information

• Verified date: January 2019
• Source: A.O. Ospedale Papa Giovanni XXIII
• Contact: ALESSANDRO RAMBALDI, MD
• Phone: 035.2673681
• Email: arambaldi[@]asst-pg23.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

MESENCHYMAL STROMAL CELLS (MSC) have shown promising albeit not always consistent therapeutic effects in the treatment of severe steroid-resistant acute Graf versus Host Disease. Remarkably, in all reported clinical studies the toxicity of Mesenchymal stromal cells administration has been found consistently negligible. The investigators believe that Umbilical Cord (UC) derived Mesenchymal stromal cells may represent a stronger immunosuppressive tool for such clinical emergency and no data suggest any change in the safety profile of these cells. For this reason, and in the best interest of the patient, the investigators plan to test the safety and activity of Umbilical Cord Mesenchymal stromal cells when given sequentially to another partially effective treatment of steroid resistant acute graf versus host disease such as Pentostatin.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 47
• Est. completion date: September 2019
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 70 Years

Eligibility

Inclusion Criteria:

Patients are required to meet the following inclusion criteria:

1. Patients with steroid refractory grade III-IV classic acute graft versus host disease (GvHD)occurring within 100 days after transplant or induced by donor lymphocyte infusions (DLI) or T-cell add back. Steroid refractory graft versus host disease (GvHD)is defined according to Pidala and Anasetti10 as follows: a) progression of at least 1 overall grade within 3 days of optimal steroid treatment; b) failure to demonstrate any overall grade improvement over 5 to 7 days; c) incomplete response by 14 days of 2 mg/kg/day of steroid therapy.

2. Patients with persistent, recurrent, or late acute graft versus host disease (GvHD) (features of acute graft versus host disease occurring beyond 100 days, often during withdrawal of immune suppression).

3. Patients with an overlap syndrome in which diagnostic or distinctive features of chronic graft versus host disease (GvHD) and acute graft versus host disease (GvHD) appear together79.

Exclusion Criteria:

1. Inability to obtain written informed consent

Related Conditions & MeSH terms

• Graft vs Host Disease
• Hematologic Malignancies

Intervention

Biological:
• UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)
pentostatin, dose 1 mg/m2 § MSC doses: 3 patients ? 3 infusions of 1x106 cells /kg 3 patients ? 3 infusions of 2x106 cells /kg 3 patients ? 3 infusions of 3x106 cells /kg

Locations

Country	Name	City	State
Italy	A O Papa Giovanni XXIII	Bergamo
Italy	Ao S Croce E Carle	Cuneo
Italy	AO Careggi	Firenze
Italy	IRCCS G Gaslini	Genova
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Italy	Clinica Pediatrica San Gerardo	Monza
Italy	Azienda Ospedaliero-Universitaria Di Udine	Udine
Italy	Ospedale San Bortolo	Vicenza

Sponsors (2)

Lead Sponsor	Collaborator
A.O. Ospedale Papa Giovanni XXIII	Associazione Italiana per la Ricerca sul Cancro

Country where clinical trial is conducted

Italy, 

References & Publications (7)

Capelli C, Gotti E, Morigi M, Rota C, Weng L, Dazzi F, Spinelli O, Cazzaniga G, Trezzi R, Gianatti A, Rambaldi A, Golay J, Introna M. Minimally manipulated whole human umbilical cord is a rich source of clinical-grade human mesenchymal stromal cells expan — View Citation

Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringdén O; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesen — View Citation

Lucchini G, Introna M, Dander E, Rovelli A, Balduzzi A, Bonanomi S, Salvadè A, Capelli C, Belotti D, Gaipa G, Perseghin P, Vinci P, Lanino E, Chiusolo P, Orofino MG, Marktel S, Golay J, Rambaldi A, Biondi A, D'Amico G, Biagi E. Platelet-lysate-expanded me — View Citation

Pérez-Simon JA, López-Villar O, Andreu EJ, Rifón J, Muntion S, Diez Campelo M, Sánchez-Guijo FM, Martinez C, Valcarcel D, Cañizo CD. Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease — View Citation

Ringdén O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lönnies H, Marschall HU, Dlugosz A, Szakos A, Hassan Z, Omazic B, Aschan J, Barkholt L, Le Blanc K. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplanta — View Citation

von Bonin M, Stölzel F, Goedecke A, Richter K, Wuschek N, Hölig K, Platzbecker U, Illmer T, Schaich M, Schetelig J, Kiani A, Ordemann R, Ehninger G, Schmitz M, Bornhäuser M. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysa — View Citation

Weiss ML, Anderson C, Medicetty S, Seshareddy KB, Weiss RJ, VanderWerff I, Troyer D, McIntosh KR. Immune properties of human umbilical cord Wharton's jelly-derived cells. Stem Cells. 2008 Nov;26(11):2865-74. doi: 10.1634/stemcells.2007-1028. Epub 2008 Aug — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	vital parameters	Following infusion of UC-MSC, the patient will be monitored for acute infusion-related toxicity. Any toxicity will be treated at the discretion of the attending physician. Infusional toxicity is defined as any alteration of the vital parameters of the patient if they have appeared acutely and may be directly correlated to the UC-MSC infusion	one year
Secondary	assessed of acute graft versus host disease (GvHD)	graft versus host disease will be assessed at day +7, +9, +12, +14, +16, +19, +21, +28, + 35, +42 e +49 and after 6 months and 1 year from the last UC-MSC infusion. Efficacy on acute graft versus host disease is defined as complete or partial resolution of acute GvHD evaluated according to conventional staging and grading score systems.The efficacy will be evaluated at day +30 after the third UC-MSC infusion or, if less, at day +30 after the last UC-MSC infusion.	one year

External Links

•   Agenzia Italiana del Farmaco (AIFA)