The primary purpose is to determine the ability of CD34+ selection and T cell depletion using the CliniMACS® device to prevent severe acute graft-versus-host disease (GVHD) in patients receiving a stem cell transplant from an alternative (unrelated and mismatched related) donor. The secondary objectives include evaluation of engraftment, immune recovery, and post-transplant infections. Patients requiring stem cell transplants for either malignant (cancerous) or non-malignant disease will be included in the study. The recipients will be grouped into one of two groups based on whether the donor is mismatched related (Cohort A) or unrelated (Cohort B). The patient will receive a conditioning regimen including chemotherapy drugs and/or total body irradiation based on the disease for which the transplant is performed.
A major issue in alternative donor (mismatched related and unrelated donor transplantation is the development of graft-versus-host disease (GVHD). Several clinical trials have shown that the use of T-cell depleted peripheral blood stem cells (PBSC) reduces GVHD in alternative donor transplants. The purpose of this study is to determine the ability of CD34 positive selection and T cell depletion using the CliniMACS® Device as the only GVHD prophylaxis to prevent severe acute GVHD in recipients of an alternative donor PBSC transplant. Mismatched related donors will match at least 3 of 6 Human leukocyte antigens(HLA)(haplocompatible) and unrelated donors will match at least 6 out of 8 HLA antigens with the transplant recipient. The conditioning therapy including chemotherapy, anti-thymocyte globulin (ATG), +/- total body irradiation (TBI) will be based on the patient's diagnosis. The transplant recipient will be followed for 5 years after transplant for GVHD, engraftment, post-transplant infections, disease relapse, and overall survival. In addition, this study will serve as a platform for a companion study of therapy to accelerate immune recovery after transplant.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.
Levine Children's Hospital, Carolinas Medical Center
Charlotte, North Carolina, United States
Number of Participants With Severe Graft vs. Host Disease (GVHD).
Severe GVHD defined as grade III/IV GVHD.
Time frame: Within 30 days after stem cell transplant
Number of Participants With Engraftment and Time to Engraftment
Engraftment was measured as time to absolute neutrophil count \>500
Time frame: Within 28 days after stem cell transplant
Number of Participants With Post-transplant Infections
Time frame: 1 year
Number of Participants With EBV-related Post Transplant Lymphoproliferative Disorder (PTLD)
Time frame: 5 years
Number of Participants With Post-transplant Leukemia Relapse
Time frame: 5 years
Number of Participants With Transplant-related Mortality
Transplant-related mortality includes death due to regimen-related toxicity or GVHD (all causes other than disease relapse). Those who died due to disease relapse are not included in the analyzed population for that time point.
Time frame: 2 year
Number of Participants With Transplant-related Toxicities
Time frame: 1 year
Overall Survival
Time frame: 2 years
Device Performance: Dose of CD34+ Cells and CD3+ Cells Given
For mismatched related donors, the target cell dose after processing is \>/= 20 x 10\^6 CD34+ cells/kg patient body weight, but \>/= 8 x 10\^6 is acceptable. For unrelated donors the target cell dose after processing is \>/= 10 x 10\^6 CD34+ cells/kg patient body weight, but \>/= 4 x 10\^6 is acceptable. The target T cell dose is \</= 3 x 10\^4 CD3+ cells/ kg.
Time frame: Length of the trial (5 years)
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