NCT02032446

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
47

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Sep 2013

Longer than P75 for phase_1

Geographic Reach
1 country

8 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2013

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

November 4, 2013

Completed
2 months until next milestone

First Posted

Study publicly available on registry

January 10, 2014

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2016

Completed
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2019

Completed
Last Updated

January 18, 2019

Status Verified

January 1, 2019

Enrollment Period

3 years

First QC Date

November 4, 2013

Last Update Submit

January 17, 2019

Conditions

Hematologic Malignancies

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • assessed of acute graft versus host disease (GvHD)

    one year

Study Arms (1)

Umbilical Cord Mesenchymal stromal cells (UC-MSC)

EXPERIMENTAL

Pentostatin will be given by intravenous infusion at a dose of 1 mg/m2 for 3 consecutive days. Thereafter, three Umbilical Cord Mesenchymal stromal cells (UC-MSC) infusions will be given at weekly interval starting from day 5. We will follow a dose escalating programme with progressively increasing doses of cells until the maximally tolerated dose (MTD) is achieved. The dose escalating design will be characterised by the administration of 1x106 /kg UC-MSC per dose per three doses for the first three patients (total up to 3x106/kg). The second three patients will receive 2x106/kg UC-MSC per dose per three doses (total up to 6x106/kg). The third three patients will receive 3x106/kg UC-MSC per dose per three doses (total up to 9x106 cells/kg). Since three dosages of cells are programmed for each group of 3 patients, a minimum of 9 patients should be studied, unless unacceptable acute infusion related toxicity is observed.

Biological: UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)

Interventions

UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)BIOLOGICAL

pentostatin, dose 1 mg/m2 § MSC doses: 1. 3 patients → 3 infusions of 1x106 cells /kg 2. 3 patients → 3 infusions of 2x106 cells /kg 3. 3 patients → 3 infusions of 3x106 cells /kg

Umbilical Cord Mesenchymal stromal cells (UC-MSC)

Eligibility Criteria

AgeUp to 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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).
  • 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.

You may not qualify if:

  • \. Inability to obtain written informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

A O Papa Giovanni XXIII

Bergamo, 24127, Italy

RECRUITING

Ao S Croce E Carle

Cuneo, 12100, Italy

RECRUITING

AO Careggi

Florence, 50134, Italy

NOT YET RECRUITING

IRCCS G Gaslini

Genova, 16147, Italy

NOT YET RECRUITING

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

ACTIVE NOT RECRUITING

Clinica Pediatrica San Gerardo

Monza, 20900, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliero-Universitaria Di Udine

Udine, 33100, Italy

NOT YET RECRUITING

Ospedale San Bortolo

Vicenza, 36100, Italy

RECRUITING

Related Publications (7)

  • 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, Ringden O; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008 May 10;371(9624):1579-86. doi: 10.1016/S0140-6736(08)60690-X.

    PMID: 18468541RESULT

  • 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 expanded in human platelet lysate. Cytotherapy. 2011 Aug;13(7):786-801. doi: 10.3109/14653249.2011.563294. Epub 2011 Mar 18.

    PMID: 21417678RESULT

  • Lucchini G, Introna M, Dander E, Rovelli A, Balduzzi A, Bonanomi S, Salvade 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 mesenchymal stromal cells as a salvage therapy for severe resistant graft-versus-host disease in a pediatric population. Biol Blood Marrow Transplant. 2010 Sep;16(9):1293-301. doi: 10.1016/j.bbmt.2010.03.017. Epub 2010 Mar 27.

    PMID: 20350611RESULT

  • Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies 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. Transplantation. 2006 May 27;81(10):1390-7. doi: 10.1097/01.tp.0000214462.63943.14.

    PMID: 16732175RESULT

  • von Bonin M, Stolzel F, Goedecke A, Richter K, Wuschek N, Holig K, Platzbecker U, Illmer T, Schaich M, Schetelig J, Kiani A, Ordemann R, Ehninger G, Schmitz M, Bornhauser M. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 2009 Feb;43(3):245-51. doi: 10.1038/bmt.2008.316. Epub 2008 Sep 29.

    PMID: 18820709RESULT

  • Perez-Simon JA, Lopez-Villar O, Andreu EJ, Rifon J, Muntion S, Diez Campelo M, Sanchez-Guijo FM, Martinez C, Valcarcel D, Canizo CD. Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica. 2011 Jul;96(7):1072-6. doi: 10.3324/haematol.2010.038356. Epub 2011 Mar 10.

    PMID: 21393326RESULT

  • 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 14.

    PMID: 18703664RESULT

Related Links

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Study Officials

  • Alessandro Rambaldi, MD

    A.O. Ospedale Papa Giovanni XXIII

    PRINCIPAL INVESTIGATOR

Central Study Contacts

ALESSANDRO RAMBALDI, MD

CONTACT

035.2673681arambaldi@asst-pg23.it

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head Hematology and Bone Marrow Transplant Unit

Study Record Dates

First Submitted

November 4, 2013

First Posted

January 10, 2014

Study Start

September 1, 2013

Primary Completion

September 1, 2016

Study Completion

September 1, 2019

Last Updated

January 18, 2019

Record last verified: 2019-01

Data Sharing

IPD Sharing
Will share

interim analysis

Locations

IT(8)