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

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

Tracking Information

• First Submitted Date: August 3, 2006
• First Posted Date: August 7, 2006
• Last Update Posted Date: November 5, 2010
• Study Start Date: September 2004
• Actual Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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: Not Provided

Current Secondary Outcome Measures (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: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer

Intervention

• 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: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 18, 2010): 49
• Original Enrollment: Not Provided
• Actual Study Completion Date: November 2010
• Actual Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00361049
• Other Study ID Numbers: 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: Not Provided
• Responsible Party: Hillard M. Lazarus, M.D., Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
• Study Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Investigators

• 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