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

NCT ID: NCT00603330

Last Updated: 2024-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2024-08-31

Brief Summary

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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.

Detailed Description

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Part 1: complete recruitment Part 2: complete recruitment Part 3: recruiting

Conditions

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Graft-versus-host Disease Poor Graft Function Low Donor T-cell Chimerism

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Mesenchymal stem cells

Intervention Type BIOLOGICAL

Mesenchymal Stem Cell infusion

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.

Group Type EXPERIMENTAL

Mesenchymal stem cells

Intervention Type BIOLOGICAL

Mesenchymal Stem Cell infusion

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.

Group Type EXPERIMENTAL

Mesenchymal stem cells

Intervention Type BIOLOGICAL

Mesenchymal Stem Cell infusion

Interventions

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Mesenchymal stem cells

Mesenchymal Stem Cell infusion

Intervention Type BIOLOGICAL

Eligibility Criteria

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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%.


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

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


1. HIV positive
2. Known allergy to Lidocaine
3. If donor other than HSC donor : any risk factor for transmissible infectious diseases.
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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KU Leuven

OTHER

Sponsor Role collaborator

Maastricht University Medical Center

OTHER

Sponsor Role collaborator

Ziekenhuis Netwerk Antwerpen (ZNA)

OTHER

Sponsor Role collaborator

University Hospital, Antwerp

OTHER

Sponsor Role collaborator

University Hospital, Ghent

OTHER

Sponsor Role collaborator

AZ-VUB

OTHER

Sponsor Role collaborator

AZ Sint-Jan AV

OTHER

Sponsor Role collaborator

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role collaborator

University Hospital of Mont-Godinne

OTHER

Sponsor Role collaborator

Jolimont Hospital Haine Saint Paul

UNKNOWN

Sponsor Role collaborator

Queen Fabiola Children's University Hospital

OTHER

Sponsor Role collaborator

University of Liege

OTHER

Sponsor Role lead

Responsible Party

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Yves Beguin

Prof

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yves Beguin, MD, PhD

Role: STUDY_CHAIR

CHU-ULg

Frédéric Baron, MD, PhD

Role: STUDY_CHAIR

CHU-ULg

Johan Maertens, MD

Role: PRINCIPAL_INVESTIGATOR

KU Leuven

Harry Schouten, MD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Pierre Zachée, MD

Role: PRINCIPAL_INVESTIGATOR

Stuyvenberg Hospital Antwerpen

Zwi Berneman, MD

Role: PRINCIPAL_INVESTIGATOR

UZA Antwerpen

Lucien Noens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UZ-Gent

Rick Schots, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

AZ VUB Jette

Dominik Selleslag, MD

Role: PRINCIPAL_INVESTIGATOR

AZ St. Jan Bugge

Augustin Ferrant, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UCL St. Luc Brussels

Chantal Doyen, MD

Role: PRINCIPAL_INVESTIGATOR

Cliniques Universitaires Mont-Godinne at Yvoir

Nicole Straetmans, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital de Jolimont at Haine-St-Paul

Nicole Ferster, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital des enfants Reine Fabiola at Brussels

Locations

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UZA

Edegem, Antwerpen, Belgium

Site Status RECRUITING

Hôpital des enfants Reine Fabiola

Brussels, Brabant, Belgium

Site Status RECRUITING

AZ VUB Jette

Brussels, Brabant, Belgium

Site Status RECRUITING

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brussels, Brabant, Belgium

Site Status RECRUITING

AZ Gasthuisberg Leuven

Leuven, Flamish Brabant, Belgium

Site Status RECRUITING

UZ Gent

Ghent, Flanders Ost, Belgium

Site Status RECRUITING

Hôpital de Jolimont

Haine-Saint-Paul, Hainaut, Belgium

Site Status RECRUITING

Cliniques Universitaires Mont-Godinne

Yvoir, Namur, Belgium

Site Status RECRUITING

AZ St Jan

Bruges, West Flanders, Belgium

Site Status RECRUITING

Hôpital Stuyvenberg

Antwerp, , Belgium

Site Status RECRUITING

CHU Sart Tilman

Liège, , Belgium

Site Status RECRUITING

University Hospital Maastricht

Maastricht, Limburg, Netherlands

Site Status NOT_YET_RECRUITING

Countries

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Belgium Netherlands

Central Contacts

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Yves Beguin, MD, PhD

Role: CONTACT

32-4-366 72 01

Frederic Baron, MD, PhD

Role: CONTACT

32-4-366 72 01

Facility Contacts

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Zwi Berneman, MD, PhD

Role: primary

32(03)8213250

Alice Ferster, MD

Role: primary

32(02)4773283

Rik Schots, MD, PhD

Role: primary

32 (02) 4763105

Augustin Ferrant, MD, PhD

Role: primary

32 (02) 7641880

Johan Maertens, MD

Role: primary

32- 16 33 22 11

Koen Theunissen, MD

Role: backup

32- 16 33 22 11

Lucien Noens, MD, PhD

Role: primary

32(09) 332 21 31

Nicole Straetmans, MD

Role: primary

32(064) 235071

Chantal Doyen, MD

Role: primary

32(081)423831

Domonik Selleslag, MD

Role: primary

32 (050) 453060

Pierre Zachée, MD, PhD

Role: primary

32(03)2177111

Yves Beguin, MD/PhD

Role: primary

32-4-366 72 01

Frederic Baron, MD/PhD

Role: backup

32-4-366 72 01

Harry Schouten, MD

Role: primary

+31-43-3876543

Other Identifiers

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TJB0703P1

Identifier Type: -

Identifier Source: org_study_id

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