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

NCT ID: NCT00361049

Last Updated: 2010-11-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-09-30

Study Completion Date

2010-11-30

Brief Summary

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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

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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.

Conditions

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Cancer

Keywords

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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 noncontiguous stage II grade 3 follicular lymphoma noncontiguous stage II mantle cell lymphoma noncontiguous stage II marginal zone lymphoma noncontiguous stage II small lymphocytic lymphoma poor prognosis metastatic gestational trophoblastic tumor previously treated myelodysplastic syndromes secondary acute myeloid leukemia secondary myelodysplastic syndromes splenic marginal zone lymphoma stage I multiple myeloma stage II multiple myeloma stage II ovarian epithelial cancer stage III adult Burkitt lymphoma stage III adult Hodgkin lymphoma stage III adult diffuse large cell lymphoma stage III adult diffuse mixed cell lymphoma stage III adult diffuse small cleaved cell lymphoma stage III adult immunoblastic large cell lymphoma stage III adult lymphoblastic lymphoma stage III chronic lymphocytic leukemia stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage III mantle cell lymphoma stage III marginal zone lymphoma stage III multiple myeloma stage III ovarian epithelial cancer stage III small lymphocytic lymphoma stage III malignant testicular germ cell tumor stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer stage IV adult Burkitt lymphoma stage IV adult Hodgkin lymphoma stage IV adult diffuse large cell lymphoma stage IV adult diffuse mixed cell lymphoma stage IV adult diffuse small cleaved cell lymphoma stage IV adult immunoblastic large cell lymphoma stage IV adult lymphoblastic lymphoma stage IV breast cancer stage IV chronic lymphocytic leukemia stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma stage IV mantle cell lymphoma stage IV marginal zone lymphoma stage IV ovarian epithelial cancer stage IV small lymphocytic lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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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.

Intervention Type BIOLOGICAL

fluorescence in situ hybridization

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

Intervention Type GENETIC

immunoenzyme technique

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

Intervention Type OTHER

immunohistochemistry staining method

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

Intervention Type OTHER

laboratory biomarker analysis

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

Intervention Type OTHER

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.

Intervention Type PROCEDURE

management of therapy complications

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

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Principal Investigators

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Hillard M. Lazarus, MD

Role: PRINCIPAL_INVESTIGATOR

Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center

Locations

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Geauga Regional Hospital

Cleveland, Ohio, United States

Site Status

Lake/University Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

University Suburban Health Center

Cleveland, Ohio, United States

Site Status

UHHS Chagrin Highlands Medical Center

Cleveland, Ohio, United States

Site Status

Southwest General Health Center

Cleveland, Ohio, United States

Site Status

UHHS Westlake Medical Center

Cleveland, Ohio, United States

Site Status

Mercy Cancer Center at Mercy Medical Center

Cleveland, Ohio, United States

Site Status

Countries

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United States

Other Identifiers

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P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE-CWRU-3Y03

Identifier Type: OTHER

Identifier Source: secondary_id

CWRU3Y03

Identifier Type: -

Identifier Source: org_study_id