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Treatment of Steroid Resistant GVHD by Infusion MSC (MSCforGVHD)

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ClinicalTrials.gov Identifier: NCT00827398
Recruitment Status : Completed
First Posted : January 22, 2009
Last Update Posted : November 6, 2014
Sponsor:
Information provided by (Responsible Party):
N.M. Wulffraat, UMC Utrecht

Brief Summary:

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 or disease Intervention/treatment Phase
Graft-versus-host-disease Biological: MSC (hPPL) Phase 1 Phase 2

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 50 patients (adults and children) with GvHD exerted by MSC expanded with human platelet lysate and plasma


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : January 2009
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013



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


Primary Outcome Measures :
  1. number of adverse events after infusion of MSC (hPPL) [ Time Frame: 6 months ]
  2. Number of severe infections after MSC infusion [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Response of acute GVHD [ Time Frame: 6 months ]
  2. Determination of incidence of chronic GVHD [ Time Frame: 6 months ]
  3. Survival [ Time Frame: 6 months ]


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Ages Eligible for Study:   1 Month to 68 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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. MSC donors can be 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00827398


Locations
Netherlands
UMC Utrecht, department of pediatrics
Utrecht, Netherlands, 3508AB
UMCU department of Haematology
Utrecht, Netherlands, 3584AB
Sponsors and Collaborators
N.M. Wulffraat
Investigators
Principal Investigator: Nico M Wulffraat UMC Utrecht
Principal Investigator: Jurgen H Kuball, MD UMC Utrecht

Responsible Party: N.M. Wulffraat, MD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT00827398     History of Changes
Other Study ID Numbers: NL13729.000.07
First Posted: January 22, 2009    Key Record Dates
Last Update Posted: November 6, 2014
Last Verified: November 2014

Keywords provided by N.M. Wulffraat, 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