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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00361049
First received: August 3, 2006
Last updated: November 4, 2010
Last verified: November 2010
  Purpose

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.


Condition Intervention Phase
Cancer
Biological: graft versus host disease prophylaxis/therapy
Genetic: fluorescence in situ hybridization
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: in vitro-treated bone marrow transplantation
Procedure: management of therapy complications
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 49
Study Start Date: September 2004
Study Completion Date: November 2010
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00361049

Locations
United States, Ohio
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Geauga Regional Hospital
Cleveland, Ohio, United States, 44024
Lake/University Ireland Cancer Center
Cleveland, Ohio, United States, 44060
Mercy Cancer Center at Mercy Medical Center
Cleveland, Ohio, United States, 44708
Southwest General Health Center
Cleveland, Ohio, United States, 44130
UHHS Chagrin Highlands Medical Center
Cleveland, Ohio, United States, 44122
UHHS Westlake Medical Center
Cleveland, Ohio, United States, 44145
University Suburban Health Center
Cleveland, Ohio, United States, 44121
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Hillard M. Lazarus, MD Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Hillard M. Lazarus, M.D., Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00361049     History of Changes
Other Study ID Numbers: CWRU3Y03, P30CA043703, CASE-CWRU-3Y03
Study First Received: August 3, 2006
Last Updated: November 4, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Graft vs Host Disease
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Immune System Diseases
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders

ClinicalTrials.gov processed this record on August 21, 2014