Donor T Cells in Treating Patients With High-Risk Hematologic Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant
RATIONALE: A donor peripheral stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of donor T cells may helps stop the patient's immune system from rejecting the donor's stem cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of donor T cells in treating patients with high-risk hematologic cancer who are undergoing donor peripheral blood stem cell transplant.
Note: Only Phase I portion of study was performed. Due to slow accrual, study was closed before Phase II portion of study.
Graft Versus Host Disease
Multiple Myeloma and Plasma Cell Neoplasm
Biological: CD4+CD25+ regulatory T cells
Procedure: allogeneic hematopoietic stem cell transplantation
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I-II Dose Escalation Study of CD4+CD25+ Cells in Adult Patients Undergoing HLA-Identical Sibling Donor Peripheral Blood Progenitor Cell Transplantation|
- Maximum tolerated dose of CD4+CD25+ cells/kg (phase I) [ Time Frame: Day 0 (48 hours post infusion) ] [ Designated as safety issue: Yes ]
- Incidence of grade 3-5 infusional toxicity (phase II) [ Time Frame: Day 0 (48 hours post infusion) ] [ Designated as safety issue: Yes ]
- Cumulative incidence of grade II-IV acute graft-versus-host-disease (GVHD) [ Time Frame: Day 100 Post Infusion ] [ Designated as safety issue: Yes ]
- Incidence of chronic graft-versus-host disease (GVHD) [ Time Frame: Month 6 Post Infusion ] [ Designated as safety issue: Yes ]
- Incidence of Relapse [ Time Frame: Month 6 Post Infusion ] [ Designated as safety issue: No ]
- Overall Survival [ Time Frame: Day 100 and 1 Year Post Infusion ] [ Designated as safety issue: No ]
- Disease-free survival [ Time Frame: Day 100 and 1 Year Post Infusion ] [ Designated as safety issue: No ]
|Study Start Date:||June 2008|
|Study Completion Date:||April 2010|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Experimental: Patients Receiving CD4+/CD25+ cells
CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant)
Biological: CD4+CD25+ regulatory T cells
Cohort 1 will receive 3 x 10^6 CD4+CD25+ cells/kg, Cohort 2 will receive 1 x 10^7 CD4+CD25+ cells/kg, Cohort 3 will receive 3 x 10^7 CD4+CD25 cells/kg
Other Name: CD4+CD25+ regulatory T cellsProcedure: allogeneic hematopoietic stem cell transplantation
Occurs on Day 0 of study - HLA-identical sibling donor peripheral blood progenitor cell (PBPC) transplantation
Other Name: peripheral blood progenitor cell (PBPC) transplantation
- To determine the maximum tolerated dose (MTD) of CD4+/CD25+ cells that can be safely administered to patients undergoing HLA-identical sibling donor Peripheral Blood Progenitor Cell (PBPC) transplantation.
- To determine whether CD4+ and CD25+ cells can be safely administered to patients with high-risk hematologic malignancies undergoing HLA-identical sibling donor PBPC transplantation.
- To determine the incidence of grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, relapse, and survival after administration of CD4+ and CD25+ regulatory T cells in these patients.
OUTLINE: This is a dose-escalation study of CD4+ and CD25+ donor regulatory T cells followed by a phase II study. All patients receive myeloablative preparative therapy and GVHD prophylaxis as per University of Minnesota protocol UMN-MT2001-02 or UMN-MT2001-10.
- First allogeneic peripheral blood progenitor cell (PBPC) infusion: Patients receive unmobilized, culture-expanded, CD4- and CD25-positive donor regulatory T cells IV over 15-60 minutes at the assigned dose on day -2.
- Second allogeneic PBPC infusion: Patients undergo matched-sibling donor PBPC transplantation IV on day 0.
Patients undergo blood sample collection prior to commencement of preparative therapy and then at day 100, 6 months, and 1 year after PBPC transplantation. Samples are analyzed for immune reconstitution by immunophenotyping and functional analyses.
After completion of study therapy, patients are followed for up to 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00725062
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Margaret L. MacMillan, MD||Masonic Cancer Center, University of Minnesota|