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

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Completed; Phase 1

Conditions: Cancer

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00361049

P30CA043703 (U.S. NIH Grant/Contract)

CASE-CWRU-3Y03 (Other Identifier)

CWRU3Y03

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)