This phase II trial tests how well removing CD45RA positive naive T cells works to prevent graft versus host disease in older patients undergoing standard of care allogeneic hematopoietic stem cell transplantation for the treatment of acute leukemia or myelodysplastic syndrome (MDS). Allogeneic hematopoietic stem cell transplantation is when healthy cells are collected from a donor and infused into a patient to help the patient's bone marrow make more healthy cells and platelets and help destroy any remaining cancer cells. Giving chemotherapy and total-body irradiation before a stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Removing the T cells from the donor cells before the transplant may stop this from happening. Giving CD45RA positive naive T cell depleted allogenic hematopoietic stem cell transplant may prevent graft versus host disease while treating acute leukemia or myelodysplastic syndrome in older adults.
OUTLINE: Patients receive cyclophosphamide intravenously (IV), over 1-2 hours on days -6 and -5, fludarabine IV, over 30 minutes on days -6 to -2 and total body irradiation for 1 treatment on day -1 or 0. Patients receive CD34+ enriched peripheral blood stem cells and CD45RA+ depleted cells IV on day 0. Patients undergo bone marrow aspiration/biopsy, echocardiography, and blood sample collection throughout the study. After completion of study treatment, patients are followed up at day 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, then weekly until 1 completion of year 1 as well as at day 180 and 270, at 1.5 and 2 years and then periodically until 5 years post day 0.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
52
Given IV
Undergo blood sample collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Given IV
Given IV
Undergo total-body irradiation
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Graft versus host disease (GVHD) relapse-free survival
Defined as duration between date of transplant and documentation of the date of first occurrence of: relapse, grade III-IV acute GVHD, chronic GVHD, or death due to any cause. Will be estimated using the method of Kaplan Meier. Ninety percent confidence intervals (to be consistent with 1-sided 5% testing) around proportions at milestone time points (e.g. 1-year) will be calculated using the log-log transformation.
Time frame: At 1 year
Overall survival
Defined as duration from date of transplant to date of death due to any cause. Will be estimated using the method of Kaplan Meier. Ninety percent confidence intervals (to be consistent with 1-sided 5% testing) around proportions at milestone time points (e.g. 1-year) will be calculated using the log-log transformation.
Time frame: At day 365 and 730 days post transplant
Time to relapse
Defined as duration date of transplant to first documentation of \>/=5% leukemic blasts by morphology in bone marrow, circulating leukemic blasts or extramedullary disease (extramedullary disease definite i.e., proven by biopsy or probably based on clinical assessment if biopsy not feasible).
Time frame: At 1 year post transplant
Treatment related mortality
Defined as death deemed related to transplant and not attributable to the underlying disease. Proportions and their associated 90% confidence intervals will be estimated, confidence intervals will be estimated using the Wilson Score method.
Time frame: At day 100 and 365 days post transplant
Graft rejection or graft failure rate
Graft failure will be operationally defined as failure to achieve an absolute neutrophil count (ANC) ≥ 0.5 × 10\^9/L before death or second transplant, or decrease to absolute neutrophil count \< 0.1 × 10\^9/L for 14 consecutive days (date of graft failure defined as the 14th day) after an established donor graft despite daily administration of granulocyte colony stimulating factor (G-CSF) and ≤ 20% bone marrow cellularity on bone marrow aspirate or biopsy any time in the first 2 years following transplant. Graft rejection will be defined by \< 5% of donor T cell (CD3+) chimerism in the absence of relapse.
Time frame: Two years post transplant
Incidence of acute GVHD
Proportions and their associated 90% confidence intervals will be estimated, confidence intervals will be estimated using the Wilson Score method.
Time frame: At day 100, 180 and 365 post transplant
Incidence of chronic GVHD
The Fine-Gray method will be used. Incidence proportions along with 90% confidence intervals will be estimated.
Time frame: At day 365 and 730 post transplant
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