NCT00361049

Donor Mesenchymal Stem Cell Infusion in Treating Patients With Acute or Chronic Graft-Versus-Host Disease After Undergoing a Donor Stem Cell Transplant

Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 49 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Cancer

Interventions

Type	Name	Description
BIOLOGICAL	graft versus host disease prophylaxis/therapy	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.
GENETIC	fluorescence in situ hybridization	Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
OTHER	immunoenzyme technique	Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
OTHER	immunohistochemistry staining method	Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
OTHER	laboratory biomarker analysis	Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
PROCEDURE	in vitro-treated bone marrow transplantation	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.
PROCEDURE	management of therapy complications	Patients will be evaluated for clinical signs and symptoms of GVHD weekly for up to 28 days.

Timeline

• Start date: 2004-09-01
• Primary completion: 2009-06-01
• Completion: 2010-11-01
• First posted: 2006-08-07
• Last updated: 2010-11-05

Locations

8 sites across 1 country: United States