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

NCT00361049 | Completed Phase 1 DMC

• 3 other identifiers: CWRU3Y03P30CA043703CASE-CWRU-3Y03
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 8

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.

Conditions

Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Safety

  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 (2)

• Complete and partial resolution of graft-vs-host disease (GVHD)

  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

  Pre-transplant, at diagnosis, 7 and 14 days after MSC infusion

Interventions

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

Geauga Regional Hospital

Cleveland, Ohio, 44024, United States

Location

Lake/University Ireland Cancer Center

Cleveland, Ohio, 44060, United States

Location

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

Cleveland, Ohio, 44106-5065, United States

Location

University Suburban Health Center

Cleveland, Ohio, 44121, United States

Location

UHHS Chagrin Highlands Medical Center

Cleveland, Ohio, 44122, United States

Location

Southwest General Health Center

Cleveland, Ohio, 44130, United States

Location

UHHS Westlake Medical Center

Cleveland, Ohio, 44145, United States

Location

Mercy Cancer Center at Mercy Medical Center

Cleveland, Ohio, 44708, United States

Location

MeSH Terms

Conditions

Neoplasms; Graft vs Host Disease; Congenital Abnormalities; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Blast Crisis; Pdgfra-Associated Chronic Eosinophilic Leukemia; Primary Myelofibrosis; Leukemia, Myelomonocytic, Chronic; Leukemia, Neutrophilic, Chronic; Leukemia, Myeloid, Chronic-Phase; Myeloproliferative Disorders; Lymphoma, B-Cell, Marginal Zone; Multiple Myeloma; Carcinoma, Ovarian Epithelial; Burkitt Lymphoma; Hodgkin Disease; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Testicular Neoplasms; Breast Neoplasms

Interventions

Therapeutics; In Situ Hybridization, Fluorescence; Immunoenzyme Techniques; Immunohistochemistry

Condition Hierarchy (Ancestors)

Immune System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Lymphoma, B-Cell; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Leukemia, Lymphoid; Leukemia, B-Cell; Genital Neoplasms, Male; Genital Diseases, Male; Male Urogenital Diseases; Testicular Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Histocytochemistry

Study Officials

• Hillard M. Lazarus, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 3, 2006
• First Posted: August 7, 2006
• Study Start: September 1, 2004
• Primary Completion: June 1, 2009
• Study Completion: November 1, 2010
• Last Updated: November 5, 2010

Record last verified: 2010-11

Locations

US (8)