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NCT Number: NCT00361049

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

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.

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Key information

Conditions

Cancer Adnexal Diseases Blast Crisis Blood Protein Disorders Bone Marrow Diseases Breast Diseases Breast Neoplasms Burkitt Lymphoma Carcinogenesis Carcinoma Carcinoma, Ovarian Epithelial Cardiovascular Diseases Cell Transformation, Neoplastic Chronic Disease Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Virus Infections Disease Attributes Endocrine Gland Neoplasms Endocrine System Diseases Epstein-Barr Virus Infections Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Diseases, Male Genital Neoplasms, Female Genital Neoplasms, Male Gonadal Disorders Graft vs Host Disease Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Herpesviridae Infections Hodgkin Disease Immune System Diseases Immunoproliferative Disorders Infections Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative Leukemia, Myeloid, Chronic-Phase Leukemia, Myelomonocytic, Chronic Leukemia, Neutrophilic, Chronic Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Male Urogenital Diseases Multiple Myeloma Myelodysplastic-Myeloproliferative Diseases Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplasms, Plasma Cell Neoplastic Processes Ovarian Diseases Ovarian Neoplasms Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Pdgfra-Associated Chronic Eosinophilic Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Primary Myelofibrosis Skin Diseases Skin and Connective Tissue Diseases Testicular Diseases Testicular Neoplasms Tumor Virus Infections Urogenital Diseases Urogenital Neoplasms Vascular Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Geauga Regional Hospital, Cleveland, Ohio, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

graft versus host disease prophylaxis/therapy

Biological

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.

fluorescence in situ hybridization

Genetic

Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.

immunoenzyme technique

Other

Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.

immunohistochemistry staining method

Other

Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.

laboratory biomarker analysis

Other

Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.

in vitro-treated bone marrow transplantation

Procedure

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.

management of therapy complications

Procedure

Patients will be evaluated for clinical signs and symptoms of GVHD weekly for up to 28 days.

Primary outcomes

  1. 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 outcomes

  1. 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.

  2. 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

Sponsors and collaborators

Lead sponsor

Case Comprehensive Cancer Center

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial

Important dates

Study start
2004
Primary completion
2009
Study completion
2010
First posted
Aug 7, 2006
Registry last updated
Nov 5, 2010

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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