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

January 17, 2019 updated by: Rambaldi Alessandro, A.O. Ospedale Papa Giovanni XXIII

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

47

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Bergamo, Italy, 24127
        • Recruiting
        • A O Papa Giovanni XXIII
        • Contact:
        • Sub-Investigator:
          • Alessandra Algarotti, MD
        • Sub-Investigator:
          • Caterina Micò, MD
        • Sub-Investigator:
          • Anna Grassi, MD
      • Cuneo, Italy, 12100
        • Recruiting
        • Ao S Croce E Carle
        • Contact:
      • Firenze, Italy, 50134
      • Genova, Italy, 16147
      • Milano, Italy, 20122
        • Active, not recruiting
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
      • Monza, Italy, 20900
        • Active, not recruiting
        • Clinica Pediatrica San Gerardo
      • Udine, Italy, 33100
        • Not yet recruiting
        • Azienda Ospedaliero-Universitaria Di Udine
        • Contact:
      • Vicenza, Italy, 36100
        • Recruiting
        • Ospedale San Bortolo
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

A.O. Ospedale Papa Giovanni XXIII

Collaborators

Associazione Italiana per la Ricerca sul Cancro

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (ACTUAL)

September 1, 2016

Study Completion (ANTICIPATED)

September 1, 2019

Study Registration Dates

First Submitted

November 4, 2013

First Submitted That Met QC Criteria

January 8, 2014

First Posted (ESTIMATE)

January 10, 2014

Study Record Updates

Last Update Posted (ACTUAL)

January 18, 2019

Last Update Submitted That Met QC Criteria

January 17, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT 2012-000582-21

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

interim analysis

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hematologic Malignancies

Clinical Trials on UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Singapore

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe