Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial
- 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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Hillard M. Lazarus, MD
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
United States: Federal Government
|Mercy Cancer Center at Mercy Medical Center||Canton, Ohio 44708|
|Lake/University Ireland Cancer Center||Mentor, Ohio 44060|
|Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|
|Geauga Regional Hospital||Chardon, Ohio 44024|
|Southwest General Health Center||Middleburgh Heights, Ohio 44130|
|UHHS Chagrin Highlands Medical Center||Orange Villager, Ohio 44122|
|University Suburban Health Center||South Euclid, Ohio 44121|
|UHHS Westlake Medical Center||Westlaker, Ohio 44145|