Donor Mesenchymal Stem Cell Infusion in Treating Patients With Acute or Chronic Graft-Versus-Host Disease After Undergoing a Donor Stem Cell Transplant
- Conditions
- Cancer
- Registration Number
- NCT00361049
- Lead Sponsor
- Case Comprehensive Cancer Center
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
Primary
* 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.
Secondary
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Safety 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.
- Secondary Outcome Measures
Name Time Method Complete and partial resolution of graft-vs-host disease (GVHD) 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 Pre-transplant, at diagnosis, 7 and 14 days after MSC infusion
Trial Locations
- Locations (8)
Geauga Regional Hospital
🇺🇸Cleveland, Ohio, United States
Lake/University Ireland Cancer Center
🇺🇸Cleveland, Ohio, United States
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
UHHS Chagrin Highlands Medical Center
🇺🇸Cleveland, Ohio, United States
Mercy Cancer Center at Mercy Medical Center
🇺🇸Cleveland, Ohio, United States
Southwest General Health Center
🇺🇸Cleveland, Ohio, United States
UHHS Westlake Medical Center
🇺🇸Cleveland, Ohio, United States
University Suburban Health Center
🇺🇸Cleveland, Ohio, United States