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

NCT ID: NCT02032446

Last Updated: 2019-01-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2019-09-30

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.

Conditions

Hematologic Malignancies

Study Design

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

Study Groups

Umbilical Cord Mesenchymal stromal cells (UC-MSC)

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.

Group Type: EXPERIMENTAL

UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)

Intervention Type: 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

Interventions

UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Associazione Italiana per la Ricerca sul Cancro

OTHER

Sponsor Role: collaborator

A.O. Ospedale Papa Giovanni XXIII

OTHER

Sponsor Role: lead

Responsible Party

Rambaldi Alessandro

Head Hematology and Bone Marrow Transplant Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alessandro Rambaldi, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Ospedale Papa Giovanni XXIII

Locations

A O Papa Giovanni XXIII

Bergamo, , Italy

Site Status: RECRUITING

Ao S Croce E Carle

Cuneo, , Italy

Site Status: RECRUITING

AO Careggi

Florence, , Italy

Site Status: NOT_YET_RECRUITING

IRCCS G Gaslini

Genova, , Italy

Site Status: NOT_YET_RECRUITING

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status: ACTIVE_NOT_RECRUITING

Clinica Pediatrica San Gerardo

Monza, , Italy

Site Status: ACTIVE_NOT_RECRUITING

Azienda Ospedaliero-Universitaria Di Udine

Udine, , Italy

Site Status: NOT_YET_RECRUITING

Ospedale San Bortolo

Vicenza, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

ALESSANDRO RAMBALDI, MD

Role: CONTACT

arambaldi@asst-pg23.it

035.2673681 ext. 0039

Facility Contacts

Maria Luisa Ferrari, Study coordinator

Role: primary

mlferrari@asst-pg23.it

035.2673681 ext. 0039

NICOLA MORANDINI, MD

Role: primary

MORANDININ@GMAIL.COM

+3901716424478

Riccardo Saccardi, MD

Role: primary

riccardo.saccardi@aou.unifi.it

0557947672

Edoardo Lanino, MD

Role: primary

edoardolanino@gaslini.org

01056362405

RENATO FANIN, MD

Role: primary

RENATO.FANIN@UNIUD.IT

+39.0432559662

ROBERTO RAIMONDI, MD

Role: primary

RAIMONDI@HEMATO.VEN.IT

+39.0444753518

References

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Reference Type: RESULT

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Reference Type: RESULT

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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.

Reference Type: RESULT

PMID: 18820709 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21393326 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18703664 (View on PubMed)

Related Links

http://www.agenziafarmaco.gov.it

Agenzia Italiana del Farmaco (AIFA)

Other Identifiers

EudraCT 2012-000582-21

Identifier Type: -

Identifier Source: org_study_id