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

Sponsor

University of Liege (Other)

Overall Status

Recruiting

CT.gov ID

NCT00603330

Collaborator

KU Leuven (Other), Maastricht University Medical Center (Other), Ziekenhuis Netwerk Antwerpen (ZNA) (Other), University Hospital, Antwerp (Other), University Hospital, Ghent (Other), AZ-VUB (Other), AZ Sint-Jan AV (Other), Cliniques universitaires Saint-Luc- Université Catholique de Louvain (Other), University Hospital of Mont-Godinne (Other), Jolimont Hospital Haine Saint Paul (Other), Queen Fabiola Children's University Hospital (Other)

100

Enrollment

Locations

Arms

175

Duration (Months)

8.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Graft-versus-host Disease Poor Graft Function Low Donor T-cell Chimerism	Biological: Mesenchymal stem cells	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Jan 1, 2008

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Arm 1. Efficacy of MSC infusion as treatment for steroid-resistant grade II - IV acute GVHD. [30 days]
Arm 2. Efficacy of MSC infusion as treatment for poor graft function [180 days]
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 [180 days]

Secondary Outcome Measures

Toxicity of MSC infusion [180 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patient eligibility criteria

Male or female of any age.
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.
Any source of HSC (marrow, PBSC, cord blood) and any conditioning regimen.
Informed consent given by donor or his/her guardian if of minor age.
Additional criteria for each part of the protocol:

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

Allogeneic transplantation.
Grade II-IV acute GVHD (see appendix A for acute GVHD grading) de novo or following DLI.
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.

Ongoing therapy with Ciclosporine or Tacrolimus at therapeutic doses.
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)

Allogeneic or autologous transplantation.
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

Cytopenia duration ≥ 2 weeks beyond day 28 after autologous HCT, or day 42 (day 60 for cord blood transplantation) after allogeneic HCT.
Cytopenia is not related to CMV or other infection, myelosuppressive/toxic drugs, renal failure, peripheral cell destruction or other identifiable cause.
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

Nonmyeloablative allogeneic transplantation.
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

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

Exclusion Criteria:

Patient exclusion criteria

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

MSC donor exclusion criteria

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UZA	Edeghem	Antwerpen	Belgium	2650
2	Hôpital des enfants Reine Fabiola	Brussels	Brabant	Belgium	1020
3	AZ VUB Jette	Brussels	Brabant	Belgium	1090
4	Cliniques universitaires Saint-Luc- Université Catholique de Louvain	Brussels	Brabant	Belgium	1200
5	AZ Gasthuisberg Leuven	Leuven	Flamish Brabant	Belgium	3000
6	UZ Gent	Gent	Flanders Ost	Belgium	9000
7	Hôpital de Jolimont	Haine St Paul	Hainaut	Belgium	7100
8	Cliniques Universitaires Mont-Godinne	Yvoir	Namur	Belgium	5530
9	AZ St Jan	Brugge	West Flanders	Belgium	8000
10	Hôpital Stuyvenberg	Antwerpen		Belgium	2060
11	CHU Sart Tilman	Liege		Belgium	4000
12	University Hospital Maastricht	Maastricht	Limburg	Netherlands	6200

Sponsors and Collaborators

University of Liege
KU 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, KU 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