Mesenchymal Stem Cell Infusion as Treatment for Steroid-Resistant Acute Graft Versus Host Disease (GVHD) or Poor Graft Function

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University Hospital of Liege
Sponsor:
Collaborators:
Katholieke Universiteit Leuven
Maastricht University Medical Center
Ziekenhuis Netwerk Antwerpen (ZNA)
University Hospital, Antwerp
University Hospital, Ghent
AZ-VUB
AZ Sint-Jan AV
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
University Hospital of Mont-Godinne
Jolimont Hospital Haine Saint Paul
Queen Fabiola Children's University Hospital
Information provided by (Responsible Party):
Yves Beguin, University Hospital of Liege
ClinicalTrials.gov Identifier:
NCT00603330
First received: January 16, 2008
Last updated: January 17, 2013
Last verified: January 2013
  Purpose

The present project aims at investigating the role of MSC for the treatment of patients with

Part 1: Steroid-refractory grade II-IV acute GVHD.

Part 2: Poor graft function (PGF)

Part 3: Low or falling donor T-cell chimerism after allogeneic HCT.

This is a multicenter phase II study examining the feasibility and efficacy of this approach.


Condition Intervention Phase
Graft-versus-host Disease
Poor Graft Function
Biological: Mesenchymal stem cells
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Infusion of Mesenchymal Stem Cells as Treatment for Steroid-Resistant Grade II to IV Acute GVHD or Poor Graft Function: a Multicenter Phase II Study

Resource links provided by NLM:


Further study details as provided by University Hospital of Liege:

Primary Outcome Measures:
  • Arm 1. Efficacy of MSC infusion as treatment for steroid-resistant grade II - IV acute GVHD. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Arm 2. Efficacy of MSC infusion as treatment for poor graft function [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • Arm 3. Efficacy of MSC infusion followed by donor lymphocyte infusion for preventing graft rejection in patients with low or failing donor T-cell chimerism after allogeneic HCT [ Time Frame: 180 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity of MSC infusion [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: January 2008
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
MSC infusion for steroid-refractory grade II-IV acute GVHD. In this arm, 4 x 10E6 MSC/Kg BW of the recipient will be injected during the first hour after thawing.
Biological: Mesenchymal stem cells
Mesenchymal Stem Cell infusion
Experimental: 2
MSC infusion for poor graft function. In this arm, 2 x 10E6 MSC/Kg BW of the recipient will be injected during the first hour after thawing.
Biological: Mesenchymal stem cells
Mesenchymal Stem Cell infusion
Experimental: 3
MSC + DLI for poor donor T-cell chimerism after allogeneic HCT. In this arm, 2 x 10E6 MSC/Kg BW of the recipient will be injected during the first hour after thawing.
Biological: Mesenchymal stem cells
Mesenchymal Stem Cell infusion

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Patient eligibility criteria

  1. Male or female of any age.
  2. Previous allogeneic transplantation (related or unrelated donor, any degree of HLA matching) or autologous transplantation (for part 2 only) of HSC at any time before.
  3. Any source of HSC (marrow, PBSC, cord blood) and any conditioning regimen.
  4. Informed consent given by donor or his/her guardian if of minor age.
  5. Additional criteria for each part of the protocol:

Part 1: MSC for steroid-refractory grade II-IV acute GVHD

  1. Allogeneic transplantation.
  2. Grade II-IV acute GVHD (see appendix A for acute GVHD grading) de novo or following DLI.
  3. Acute GVHD refractory to mPDN 2 mg/kg/day or equivalent, defined as

    • progression of GVHD on day 3 after initiation of steroids
    • no improvement of GVHD on day 7 after initiation of steroids
    • absence of complete resolution of acute GVHD on day 14 after initiation of steroids
    • relapse of acute GVHD during or after steroid taper.
  4. Ongoing therapy with Ciclosporine or Tacrolimus at therapeutic doses.
  5. Patient may have received previously any other form of treatment for acute GVHD, but no new treatment started within 1 month of study entry.

Part 2: MSC for poor graft function (PGF)

  1. Allogeneic or autologous transplantation.
  2. Cytopenia in 2 or 3 lineages:

    • Hb < 8.0 g/dL and reticulocytes < 1%, with or without transfusion
    • Plt < 20,000/µL without transfusion
    • Neutrophils < 500/µL, without G-CSF administration

    OR severe cytopenia in 1 lineage:

    • RBC transfusion dependent (if autologous transplantation; despite EPO administration if allogeneic transplantation)
    • Plt transfusion dependent
    • Neutrophils < 500/µL despite G-CSF administration
  3. Cytopenia duration ≥ 2 weeks beyond day 28 after autologous HCT, or day 42 (day 60 for cord blood transplantation) after allogeneic HCT.
  4. Cytopenia is not related to CMV or other infection, myelosuppressive/toxic drugs, renal failure, peripheral cell destruction or other identifiable cause.
  5. In case of HLA-identical related donor and full donor chimerism, patient can only be included if a boost of donor CD34+ cells has been unsuccessful or is not feasible.

Part 3: MSC + DLI for poor donor T-cell chimerism

  1. Nonmyeloablative allogeneic transplantation.
  2. Donor T-cell chimerism < 50% for at least 2 consecutive weeks beyond day 21 after HCT OR

    • 20% decrease in donor T-cell chimerism with the second value < 50%.

MSC donor inclusion criteria

  1. Related to the recipient (sibling, parent or child) or unrelated.
  2. Male or female.
  3. Age > 16 yrs (no age limit if same as HSC donor).
  4. No HLA matching required.
  5. Fulfills generally accepted criteria for allogeneic HSC donation.
  6. Informed consent given by donor or his/her guardian if of minor age.

Exclusion Criteria:

Patient exclusion criteria

  1. HIV positive.
  2. Active uncontrolled infection at time of scheduled MSC infusion.
  3. Relapsing or progressing malignancy.

MSC donor exclusion criteria

  1. HIV positive
  2. Known allergy to Lidocaine
  3. If donor other than HSC donor : any risk factor for transmissible infectious diseases.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00603330

Contacts
Contact: Yves Beguin, MD, PhD 32-4-366 72 01 yves.beguin@chu.ulg.ac.be
Contact: Frederic Baron, MD, PhD 32-4-366 72 01 F.Baron@ulg.ac.be

Locations
Belgium
UZA Recruiting
Edeghem, Antwerpen, Belgium, 2650
Contact: Zwi Berneman, MD, PhD    32(03)8213250    zwi.berneman@uza.be   
Principal Investigator: Zwi Berneman, MD, PhD         
AZ VUB Jette Recruiting
Brussels, Brabant, Belgium, 1090
Contact: Rik Schots, MD, PhD    32 (02) 4763105    Rik.Schots@uzbrussel.be   
Principal Investigator: Rick Schots, MD, PhD         
Cliniques universitaires Saint-Luc- Université Catholique de Louvain Recruiting
Brussels, Brabant, Belgium, 1200
Contact: Augustin Ferrant, MD, PhD    32 (02) 7641880    Augustin.Ferrant@uclouvain.be   
Principal Investigator: Augustin Ferrant, MD, PhD         
Hôpital des enfants Reine Fabiola Recruiting
Brussels, Brabant, Belgium, 1020
Contact: Alice Ferster, MD    32(02)4773283    alice.ferster@huderf.be   
Principal Investigator: Alice Ferster, MD         
AZ Gasthuisberg Leuven Recruiting
Leuven, Flamish Brabant, Belgium, 3000
Contact: Johan Maertens, MD    32- 16 33 22 11    johan.maertens@uz.kuleuven.ac.be   
Contact: Koen Theunissen, MD    32- 16 33 22 11    koen.theunissen@uz.kuleuven.ac.be   
Principal Investigator: Johan Maertens, MD         
Principal Investigator: Koen Theunissen, MD         
UZ Gent Recruiting
Gent, Flanders Ost, Belgium, 9000
Contact: Lucien Noens, MD, PhD    32(09) 332 21 31    Lucien.Noens@Ugent.be   
Principal Investigator: Lucien Noens, MD, PhD         
Hôpital de Jolimont Recruiting
Haine St Paul, Hainaut, Belgium, 7100
Contact: Nicole Straetmans, MD    32(064) 235071    nicole.straetmans@scarlet.be   
Principal Investigator: Nicole Straetmans, MD         
Cliniques Universitaires Mont-Godinne Recruiting
Yvoir, Namur, Belgium, 5530
Contact: Chantal Doyen, MD    32(081)423831    chantal.doyen@sang.ucl.ac.be   
Principal Investigator: Chantal Doyen, MD         
AZ St Jan Recruiting
Brugge, West Flanders, Belgium, 8000
Contact: Domonik Selleslag, MD    32 (050) 453060    dominik.selleslag@azbrugge.be   
Principal Investigator: Dominik Selleslag, MD         
Hôpital Stuyvenberg Recruiting
Antwerpen, Belgium, 2060
Contact: Pierre Zachée, MD, PhD    32(03)2177111    pierre.zachee@zna.be   
Principal Investigator: Pierre Zachée, MD, PhD         
CHU Sart Tilman Recruiting
Liege, Belgium, 4000
Contact: Yves Beguin, MD/PhD    32-4-366 72 01    yves.beguin@chu.ulg.ac.be   
Contact: Frederic Baron, MD/PhD    32-4-366 72 01    F.Baron@ulg.ac.be   
Principal Investigator: Yves Beguin, MD, PhD         
Principal Investigator: Frederic Baron, MD, PhD         
Principal Investigator: Chantal Lechanteur, PhD         
Sub-Investigator: Etienne Baudoux, MD         
Sub-Investigator: Evelyne Willems, MD         
Sub-Investigator: Pascale Frère, MD, PhD         
Sub-Investigator: Bernard De Prijck, MD         
Netherlands
University Hospital Maastricht Not yet recruiting
Maastricht, Limburg, Netherlands, 6200
Contact: Harry Schouten, MD    +31-43-3876543    h.schouten@intmed.unimaas.nl   
Principal Investigator: Harry Schouten, MD         
Sponsors and Collaborators
University Hospital of Liege
Katholieke Universiteit Leuven
Maastricht University Medical Center
Ziekenhuis Netwerk Antwerpen (ZNA)
University Hospital, Antwerp
University Hospital, Ghent
AZ-VUB
AZ Sint-Jan AV
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
University Hospital of Mont-Godinne
Jolimont Hospital Haine Saint Paul
Queen Fabiola Children's University Hospital
Investigators
Study Chair: Yves Beguin, MD, PhD CHU-ULg
Study Chair: Frédéric Baron, MD, PhD CHU-ULg
Principal Investigator: Johan Maertens, MD Katholieke Universiteit Leuven
Principal Investigator: Harry Schouten, MD Maastricht University Medical Center
Principal Investigator: Pierre Zachée, MD Stuyvenberg Hospital Antwerpen
Principal Investigator: Zwi Berneman, MD UZA Antwerpen
Principal Investigator: Lucien Noens, MD, PhD UZ-Gent
Principal Investigator: Rick Schots, MD, PhD AZ VUB Jette
Principal Investigator: Dominik Selleslag, MD AZ St. Jan Bugge
Principal Investigator: Augustin Ferrant, MD, PhD UCL St. Luc Brussels
Principal Investigator: Chantal Doyen, MD Cliniques Universitaires Mont-Godinne at Yvoir
Principal Investigator: Nicole Straetmans, MD Hôpital de Jolimont at Haine-St-Paul
Principal Investigator: Nicole Ferster, MD Hôpital des enfants Reine Fabiola at Brussels
  More Information

No publications provided

Responsible Party: Yves Beguin, Prof, University Hospital of Liege
ClinicalTrials.gov Identifier: NCT00603330     History of Changes
Other Study ID Numbers: TJB0703P1
Study First Received: January 16, 2008
Last Updated: January 17, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by University Hospital of Liege:
Mesenchymal stem cells
Graft-versus-host disease
Poor graft function
Chimerism
Hematopoietic cell transplantation recipients

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

ClinicalTrials.gov processed this record on August 28, 2014