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Umbilical Cord Derived Mesenchymal Stromal Cells For The Treatment of Severe Steroid-resistant Graft Versus Host Disease (PTC-UC-MSC)

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ClinicalTrials.gov Identifier: NCT02032446
Recruitment Status : Recruiting
First Posted : January 10, 2014
Last Update Posted : April 18, 2018
Sponsor:
Collaborator:
Associazione Italiana per la Ricerca sul Cancro
Information provided by (Responsible Party):
Rambaldi Alessandro, A.O. Ospedale Papa Giovanni XXIII

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hematologic Malignancies Biological: UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC) Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : September 2013
Actual Primary Completion Date : September 2016
Estimated Study Completion Date : September 2019

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Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.

 Biological: 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


Outcome Measures
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Primary Outcome Measures :
  1. vital parameters [ Time Frame: one year ]
    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


Secondary Outcome Measures :
  1. assessed of acute graft versus host disease (GvHD) [ Time Frame: one year ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02032446


Contacts
Contact: ALESSANDRO RAMBALDI, MD 035.2673681 ext 0039 arambaldi@asst-pg23.it

Locations
Italy
A O Papa Giovanni XXIII Recruiting
Bergamo, Italy, 24127
Contact: Maria Luisa Ferrari, Study coordinator    035.2673681 ext 0039    mlferrari@asst-pg23.it   
Sub-Investigator: Alessandra Algarotti, MD         
Sub-Investigator: Caterina Micò, MD         
Sub-Investigator: Anna Grassi, MD         
Ao S Croce E Carle Recruiting
Cuneo, Italy, 12100
Contact: NICOLA MORANDINI, MD    +3901716424478    MORANDININ@GMAIL.COM   
AO Careggi Not yet recruiting
Firenze, Italy, 50134
Contact: Riccardo Saccardi, MD    0557947672    riccardo.saccardi@aou.unifi.it   
IRCCS G Gaslini Not yet recruiting
Genova, Italy, 16147
Contact: Edoardo Lanino, MD    01056362405    edoardolanino@gaslini.org   
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico Active, not recruiting
Milano, Italy, 20122
Clinica Pediatrica San Gerardo Active, not recruiting
Monza, Italy, 20900
Azienda Ospedaliero-Universitaria Di Udine Not yet recruiting
Udine, Italy, 33100
Contact: RENATO FANIN, MD    +39.0432559662    RENATO.FANIN@UNIUD.IT   
Ospedale San Bortolo Active, not recruiting
Vicenza, Italy, 36100
Sponsors and Collaborators
A.O. Ospedale Papa Giovanni XXIII
Associazione Italiana per la Ricerca sul Cancro
Investigators
Principal Investigator: Alessandro Rambaldi, MD A.O. Ospedale Papa Giovanni XXIII
More Information
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Additional Information:
Agenzia Italiana del Farmaco (AIFA)  This link exits the ClinicalTrials.gov site

Publications of Results:

Responsible Party: Rambaldi Alessandro, Head Hematology and Bone Marrow Transplant Unit, A.O. Ospedale Papa Giovanni XXIII
ClinicalTrials.gov Identifier: NCT02032446     History of Changes
Other Study ID Numbers: EudraCT 2012-000582-21
First Posted: January 10, 2014    Key Record Dates
Last Update Posted: April 18, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: interim analysis

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases