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

Primary Purpose

Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
graft versus host disease prophylaxis/therapy
fluorescence in situ hybridization
immunoenzyme technique
immunohistochemistry staining method
laboratory biomarker analysis
in vitro-treated bone marrow transplantation
management of therapy complications
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Geauga Regional Hospital
  • Lake/University Ireland Cancer Center
  • Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
  • University Suburban Health Center
  • UHHS Chagrin Highlands Medical Center
  • Southwest General Health Center
  • UHHS Westlake Medical Center
  • Mercy Cancer Center at Mercy Medical Center

Outcomes

Primary Outcome Measures

Safety

Secondary Outcome Measures

Complete and partial resolution of graft-vs-host disease (GVHD)
Cytokine levels, lymphocyte subsets, and donor-reactive lymphocyte numbers in patients with acute GVHD

Full Information

First Posted
August 3, 2006
Last Updated
November 4, 2010
Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00361049
Brief Title
Donor Mesenchymal Stem Cell Infusion in Treating Patients With Acute or Chronic Graft-Versus-Host Disease After Undergoing a Donor Stem Cell Transplant
Official Title
Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2010
Overall Recruitment Status
Completed
Study Start Date
September 2004 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
graft versus host disease prophylaxis/therapy
Intervention Description
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.
Intervention Type
Genetic
Intervention Name(s)
fluorescence in situ hybridization
Intervention Description
Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
Intervention Type
Other
Intervention Name(s)
immunoenzyme technique
Intervention Description
Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Intervention Description
Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
Intervention Type
Procedure
Intervention Name(s)
in vitro-treated bone marrow transplantation
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
management of therapy complications
Intervention Description
Patients will be evaluated for clinical signs and symptoms of GVHD weekly for up to 28 days.
Primary Outcome Measure Information:
Title
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.
Secondary Outcome Measure Information:
Title
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.
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hillard M. Lazarus, MD
Organizational Affiliation
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Geauga Regional Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44024
Country
United States
Facility Name
Lake/University Ireland Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44060
Country
United States
Facility Name
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States
Facility Name
University Suburban Health Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44121
Country
United States
Facility Name
UHHS Chagrin Highlands Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
Southwest General Health Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
Facility Name
UHHS Westlake Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44145
Country
United States
Facility Name
Mercy Cancer Center at Mercy Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44708
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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