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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

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ClinicalTrials.gov Identifier: NCT00361049
Recruitment Status : Completed
First Posted : August 7, 2006
Last Update Posted : November 5, 2010
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE August 3, 2006
First Posted Date  ICMJE August 7, 2006
Last Update Posted Date November 5, 2010
Study Start Date  ICMJE September 2004
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2010)
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. ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2010)
  • 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. ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 18, 2010)
49
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE November 2010
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00361049
Other Study ID Numbers  ICMJE CWRU3Y03
P30CA043703 ( U.S. NIH Grant/Contract )
CASE-CWRU-3Y03 ( Other Identifier: Case Comprehensive Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hillard M. Lazarus, M.D., Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Hillard M. Lazarus, MD Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date November 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP