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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

January 16, 2008
January 17, 2013
January 2008
October 2013   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT00603330 on ClinicalTrials.gov Archive Site
Toxicity of MSC infusion [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Mesenchymal Stem Cell Infusion as Treatment for Steroid-Resistant Acute Graft Versus Host Disease (GVHD) or Poor Graft Function
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

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Graft-versus-host Disease
  • Poor Graft Function
Biological: Mesenchymal stem cells
Mesenchymal Stem Cell infusion
  • 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.
    Intervention: Biological: Mesenchymal stem cells
  • 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.
    Intervention: Biological: Mesenchymal stem cells
  • 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.
    Intervention: Biological: Mesenchymal stem cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
120
April 2014
October 2013   (final data collection date for primary outcome measure)

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.
Both
Not Provided
Yes
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
Belgium,   Netherlands
 
NCT00603330
TJB0703P1
No
Yves Beguin, University Hospital of Liege
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
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
University Hospital of Liege
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP