Very Low-dose Total Body Irradiation in Combination With Total Lymphoid Irradiation and Anti-Thymocyte Globulin to Improve Donor Engraftment in Patients Undergoing Non-Myeloablative Hematopoietic Cell Transplantation
Overview
- Phase
- Phase 2
- Intervention
- Total body irradiation (TBI)
- Conditions
- Acute Myeloid Leukemia
- Sponsor
- Stanford University
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to evaluate whether addition of a low dose of total body irradiation (TBI) to a standard preparation for transplant [total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG)] conditioning will help to augment donor chimerism without reducing tolerability of this regimen or increasing the risk of graft-vs-host disease (GVHD)
Detailed Description
Primary Objective: • Determine the proportion of patients with full donor T-cell chimerism at Day 28 following hematopoietic cell transplantation. Secondary Objectives: * Determine the risk of disease progression, overall and event free survival, and non-relapse mortality, following treatment with TLI; ATG; and TBI. * Determine the incidence of acute and chronic GVHD following treatment with TLI; ATG; and TBI. Exploratory Objectives: • Determine the changes in frequency of hematopoietic stem, progenitor, and mature cell subsets and the changes in cytokine milieu and cellular architecture in the bone marrow of patients receiving TLI compared to TLI+TBI.
Investigators
Robert Lowsky
Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
Stanford University
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
TBI+TLI
TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen)
Intervention: Total body irradiation (TBI)
TBI+TLI
TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen)
Intervention: Anti-thymocyte globulin (ATG)
TBI+TLI
TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen)
Intervention: Tacrolimus
TBI+TLI
TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen)
Intervention: Mycophenolate mofetil (MMF)
TBI+TLI
TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen)
Intervention: Total lymphoid irradiation (TLI)
Outcomes
Primary Outcomes
Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.
Time Frame: Day 28
Subsequent to TLI/ATG/TBI conditioning, the proportion of participants with full dose donor chimerism (FDC) will be determined by Day 28. FDC is defined as achieving ≥ 95% donor type in the CD3+ lineage within 28 days of donor cell infusion, as assessed by short tandem repeat (STR) testing. The outcome will be expressed as the number of participants that achieve FDC by Day 28, a number without dispersion.
Secondary Outcomes
- Graft vs Host Disease (GvHD)(1 year)
- Overall Survival (OS)(1 year)
- Event-free Survival (EFS) at 1 Year(1 year)
- Disease Progression(1 year)
- Non-relapse Mortality (NRM)(1 year)