Donor Mesenchymal Stem Cell Infusion in Treating Patients With Acute or Chronic Graft-Versus-Host Disease After Undergoing a Donor Stem Cell Transplant
|ClinicalTrials.gov Identifier: NCT00361049|
Recruitment Status : Completed
First Posted : August 7, 2006
Last Update Posted : November 5, 2010
RATIONALE: Donor mesenchymal stem cell infusion may be an effective treatment for acute or chronic graft-versus-host disease caused by a donor stem cell transplant.
PURPOSE: This phase I trial is studying the side effects and best dose of donor mesenchymal stem cells in treating patients with acute or chronic graft-versus-host disease after undergoing a donor stem cell transplant.
|Condition or disease||Intervention/treatment||Phase|
|Cancer||Biological: graft versus host disease prophylaxis/therapy Genetic: fluorescence in situ hybridization Other: immunoenzyme technique Other: immunohistochemistry staining method Other: laboratory biomarker analysis Procedure: in vitro-treated bone marrow transplantation Procedure: management of therapy complications||Phase 1|
- Determine the safety of donor mesenchymal stem cell (MSC) infusion in patients with acute or extensive chronic graft-vs-host disease (GVHD) after undergoing HLA-identical sibling donor stem cell transplant.
- Describe the rates of complete and partial resolution of GVHD when MSCs are used in addition to the standard GVHD therapy.
- Determine inflammatory cytokine levels, lymphocyte subsets, and donor-reactive lymphocyte numbers in blood of patients with acute GVHD prior to therapy and at 7 and 14 days post-MSC therapy.
- Determine if donor MSCs engraft in tissues inflamed by GVHD in patients who have undergone gender-mismatched transplantation.
OUTLINE: This is a multicenter, dose-escalation study of donor mesenchymal stem cells (MSC).
Within 72 hours after the initiation of medical therapy (e.g., corticosteroids, cyclosporine) for graft-vs-host disease, patients undergo donor MSC infusion over 10-15 minutes.
Cohorts of 3-6 patients receive escalating doses of donor MSCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Blood samples are obtained periodically and examined by immunoenzyme techniques for mixed lymphocyte reaction (as a surrogate marker for alloreactivity) and cytokine levels (TH1 [i.e., interleukin (IL)-2 and interferon-gamma], TH2 [i.e., IL-10 and IL-4], and inflammatory cytokines [i.e., tumor necrosis factor-alpha and IL-1]). Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
After completion of study treatment, patients are followed periodically for 1 year.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||49 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial|
|Study Start Date :||September 2004|
|Primary Completion Date :||June 2009|
|Study Completion Date :||November 2010|
Biological: graft versus host disease prophylaxis/therapy
- Safety [ Time Frame: Monitored for 6 hours for infusion related toxicity. Temperature, blood pressure, pulse and O2 saturation will be measured at baseline and every 10 minutes x 2, every 30 minutes x 2, and every hour x 3. ]
- Complete and partial resolution of graft-vs-host disease (GVHD) [ Time Frame: Patients will be evaluated for clinical signs and symptoms of GVHD weekly for up to 28 days. ]
- Cytokine levels, lymphocyte subsets, and donor-reactive lymphocyte numbers in patients with acute GVHD [ Time Frame: Pre-transplant, at diagnosis, 7 and 14 days after MSC infusion ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00361049
|United States, Ohio|
|Geauga Regional Hospital|
|Cleveland, Ohio, United States, 44024|
|Lake/University Ireland Cancer Center|
|Cleveland, Ohio, United States, 44060|
|Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|University Suburban Health Center|
|Cleveland, Ohio, United States, 44121|
|UHHS Chagrin Highlands Medical Center|
|Cleveland, Ohio, United States, 44122|
|Southwest General Health Center|
|Cleveland, Ohio, United States, 44130|
|UHHS Westlake Medical Center|
|Cleveland, Ohio, United States, 44145|
|Mercy Cancer Center at Mercy Medical Center|
|Cleveland, Ohio, United States, 44708|
|Principal Investigator:||Hillard M. Lazarus, MD||Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center|