Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial
18 Years
N/A
Both
Cancer
Trial Information
Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Developed acute graft-vs-host disease (GVHD) of clinical grade II-IV or extensive
chronic GVHD after undergoing HLA-identical sibling donor hematopoietic stem cell
transplant for any indication, malignant or nonmalignant
- Requires systemic immunosuppressive therapy with systemic corticosteroids
(methylprednisone dose 2 mg/kg/day or equivalent) and concurrent cyclosporine or
tacrolimus
- May have been enrolled on an institutional allogeneic stem cell transplant protocol
using either ablative or nonmyeloablative preparative regimens
- No evidence of relapsed or progressive malignant disease at the time of GVHD
PATIENT CHARACTERISTICS:
- Not pregnant
- Negative pregnancy test
- Creatinine clearance ≥ 20 mL/min
- Oxygen saturation ≥ 90% on room air
- No severe or symptomatic restrictive or obstructive lung disease or respiratory
failure requiring ventilator support
- No uncontrolled hypertension or congestive heart failure, active angina pectoris
requiring the use of nitrates, myocardial infarction within the past 6 months, or
major ventricular arrhythmia or cardiac failure requiring active treatment
- No significant organ dysfunction
- No active severe infections, including sepsis, pneumonia with hypoxemia, persistent
bacteremia, or meningitis
- Fever without a source is allowed
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety
Outcome 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.
Safety Issue:
Yes
Principal Investigator
Hillard M. Lazarus, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CWRU3Y03
NCT ID:
NCT00361049
Start Date:
September 2004
Completion Date:
November 2010
Related Keywords:
- Cancer
- graft versus host disease
- unspecified adult solid tumor, protocol specific
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- accelerated phase chronic myelogenous leukemia
- adult acute lymphoblastic leukemia in remission
- adult acute myeloid leukemia in remission
- atypical chronic myeloid leukemia
- blastic phase chronic myelogenous leukemia
- chronic eosinophilic leukemia
- primary myelofibrosis
- chronic myelomonocytic leukemia
- chronic neutrophilic leukemia
- chronic phase chronic myelogenous leukemia
- de novo myelodysplastic syndromes
- disseminated neuroblastoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- myelodysplastic/myeloproliferative disease, unclassifiable
- nodal marginal zone B-cell lymphoma
- noncontiguous stage II adult Burkitt lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult diffuse mixed cell lymphoma
- noncontiguous stage II adult diffuse small cleaved cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 3 follicular lymphoma
- noncontiguous stage II mantle cell lymphoma
- noncontiguous stage II marginal zone lymphoma
- noncontiguous stage II small lymphocytic lymphoma
- poor prognosis metastatic gestational trophoblastic tumor
- previously treated myelodysplastic syndromes
- secondary acute myeloid leukemia
- secondary myelodysplastic syndromes
- splenic marginal zone lymphoma
- stage I multiple myeloma
- stage II multiple myeloma
- stage II ovarian epithelial cancer
- stage III adult Burkitt lymphoma
- stage III adult Hodgkin lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III chronic lymphocytic leukemia
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III mantle cell lymphoma
- stage III marginal zone lymphoma
- stage III multiple myeloma
- stage III ovarian epithelial cancer
- stage III small lymphocytic lymphoma
- stage III malignant testicular germ cell tumor
- stage IIIA breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- stage IV adult Burkitt lymphoma
- stage IV adult Hodgkin lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV breast cancer
- stage IV chronic lymphocytic leukemia
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV mantle cell lymphoma
- stage IV marginal zone lymphoma
- stage IV ovarian epithelial cancer
- stage IV small lymphocytic lymphoma
- Graft vs Host Disease
- Lymphoma, Non-Hodgkin
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| 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 |
