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Treatment of Steroid Resistant GVHD by Infusion MSC (MSCforGVHD)

This study is currently recruiting participants.
Verified August 2011 by UMC Utrecht
Sponsor:
Information provided by (Responsible Party):
N.M. Wulffraat, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00827398
First received: January 20, 2009
Last updated: August 23, 2011
Last verified: August 2011
History of Changes
  Purpose

For numerous malignant diseases allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy. One of the major complications is the occurrence of acute graft-versus-host-disease (aGVHD). Thirty to eighty percent of patients after HSCT develop aGVHD despite the prophylactic application of different immunosuppressive drugs.

The response rates to the conventional first line treatment are only 15-35%4. In case of a steroid refractory aGVHD different therapeutic strategies have been evaluated, but with no satisfactory results so far. The mortality of patients suffering from steroid refractory aGVHD remains at 75-80%. Therefore, it remains important to search for new therapeutical strategies for the treatment of aGVHD.


Condition Intervention Phase
Graft-versus-host-disease
 Biological: MSC (hPPL)
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Steroid Resistant Grade II to IV GVHD by Infusion MSCof Mesenchymal Stem Cells Expanded With Human Plasma and Platelet Lysate a Phase I/II Study

Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • number of adverse events after infusion of MSC (hPPL) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Number of severe infections after MSC infusion [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response of acute GVHD [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Determination of incidence of chronic GVHD [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: January 2009
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: MSC (hPPL)
    Treatment with MSCs (hPPL) is indicated as soon as steroid refractory acute GVHD is diagnosed
    Other Name: Mesenchymal Stem Cells
Detailed Description:

For numerous malignant and non-malignant hematological diseases allogeneic hemato¬poietic stem cell transplantation (HSCT) is the only curative therapy. One of the major complications is the occurrence of acute graft-versus-host-disease (aGVHD). Thirty to eighty percent of patients after HSCT develop aGVHD despite the prophylactic application of different immunosuppressive drugs depending on risk factors such as HLA-match, donor relation, age etc.1-3.

First line therapy of aGVHD > grade I consists of steroids at a dose of 2 mg/kg. The response rates to this treatment are only 15-35%4. In case of a steroid refractory aGVHD different therapeutic strategies have been evaluated, but with no satisfactory results so far. The mortality of patients suffering from steroid refractory aGVHD remains at 75-80%, although numerous studies with different treatment strategies have been conducted2-5. Therefore, it remains important to search for new therapeutical strategies for the treatment of aGVHD.

The first patient to receive mismatched Mesenchymal Stem Cells was a twenty-year-old woman with acute myeloid leukemia treated with peripheral blood stem cells combined with MSC from her haploidentical father. Lazarus et al. reported on 46 patients who received HSCs and culture-expanded MSCs from HLA-identical siblings. Moderate to severe acute GvHD was observed in 28% of the patients, and chronic GvHD was seen in 61%. The two-year progression-free survival was observed in 53% of the patients. MSC infusion caused no acute or long-term MSC-associated adverse events.

Traditionally, for MSC isolation and expansion, fetal calf serum (FCS) supplemented media are used. The use of FCS has however several drawbacks and potential problems. We have therefore established a MSC culture protocol in animal serum free conditions using human platelet lysate and human plasma instead.

The present phase I/II study is designed to gather further insight into the clinical benefit in 10 patients (adults and children) with GvHD exerted by MSC expanded with human platelet lysate and plasma

  Eligibility

Ages Eligible for Study:   1 Month to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed acute grade II-IV GVHD or chronic GVHD with an acute pattern matching grade II-IV after allogeneic stem cell transplantation
  • Patients must have received 2 mg/kg/day of prednisolon for at least 3 consecutive days and experience progression of GVHD or no response to at least 7 days of steroid treatment.
  • In addition to steroids the patient has received either cyclosporin
  • Written informed consent
  • MSC donor must be HIV, HTLV, hepatitis BS antigen, HCV and HBC, Treponema Pallidum antibody negative and match in CMV status with the recipient.First choice is the original stem cell donor or an HLA-identical sibling donor, Second choice HLA-haploidentical related donor, Third choice mismatched related donor, Third party matched or mismatched donor.

Exclusion Criteria:

  • Patients with poor performance, not expected to survive 3 weeks.
  • Donor Chimerism below 90%
  • Active uncontrolled CMV, EBV or fungal infection
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00827398

Contacts
Contact: Nico M Wulffraat, MD, PhD (31)88-7554003 n.wulffraat@umcutrecht.nl
Contact: Jurgen HE Kuball, MD,PhD (31)88-7554982 J.H.E.Kuball@umcutrecht.nl

Locations
Netherlands
UMC Utrecht, department of pediatrics Not yet recruiting
Utrecht, Netherlands, 3508AB
Contact: Nico M Wulffraat         n.wulffraat@umcutrecht.nl    
Principal Investigator: Nico M Wulffraat, MD            
UMCU department of Haematology Recruiting
Utrecht, Netherlands, 3584AB
Contact: Jurgen Kuball, MD     (31)88.7554982     j.h.e.kuball@umcutrecht.nl    
Sponsors and Collaborators
N.M. Wulffraat
Investigators
Principal Investigator: Nico M Wulffraat UMC Utrecht
Principal Investigator: Jurgen H Kuball, MD UMC Utrecht
  More Information

No publications provided

Responsible Party: N.M. Wulffraat, MD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT00827398     History of Changes
Other Study ID Numbers: NL13729.000.07
Study First Received: January 20, 2009
Last Updated: August 23, 2011
Health Authority: Netherlands: Ministry of Health, Welfare and Sport

Keywords provided by UMC Utrecht:
MSC
GVHD
Adults
Children
steroid refractory acute GVHD occurring after allogeneic stem cell transplantation

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

ClinicalTrials.gov processed this record on May 21, 2013