Phase II Clinical Trial of 2 Step ATG Combined With Tacrolimus and Mini Methotrexate for Prevention of Acute GVHD Post Myeloablative Allogeneic Stem Cell Transplant
University of Alabama at Birmingham
Summary
The purpose of this study is to test whether the combination of the drugs called tacrolimus (Tac), methotrexate (MTX) and new dosing strategy of another drug called (rabbit Anti-thymocyte Globulin \[ATG\]) will help prevent the development and/or improve severity of acute and/or chronic GVHD.
Description
The goal is to study the effectiveness and drug levels of new dosing strategy of ATG (GVHD preventing medicine) in preventing graft versus host disease post allogeneic stem cell transplantation. In an effort to reduce graft versus host disease (GVHD) and enhance graft versus leukemia (GVL) effect post allogenic hematopoietic stem cell transplantation (AHSCT), recent research has focused on host immune cell depletion. Frame shifting anti-thymocyte globulin (ATG) backwards to earlier days before days 0 can result in deeper host and less graft T-cell depletion, leading to better immune reconstit…
Eligibility
- Age range
- 18–60 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Adult male or female, age 18-60 years 2. Patients must have a related or unrelated peripheral blood stem cell donor. Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation. Unrelated donor must be 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate s…
Interventions
- DrugATG Combined with Tacrolimus and Mini Methotrexate
On Day -7, subjects will be admitted to the hospital and receive a dose of prednisone at 1 mg/kg (ATG premedication). Subjects will receive a steroid injection 3 hours before every ATG infusion. On day -6, subjects will receive a small dose of ATG as an IV infusion. ATG will be repeated on days -5,-4 and -1. Routine transplant chemotherapy agent fludarabine will be given on days -6 to -2 as daily IV infusions. Busulfan, a routine transplant chemotherapy will be given on days -5 to -2 as IV infusion. Subjects with lymphoblastic leukemia will receive an alternative regimen of cyclophosphamide, a routine chemotherapy on days -6 and -5, followed by total body radiation on days -3 to -1. Tacrolimus (standard immune suppression agent) starts on day -3 as continuous IV infusion and switched to oral after engraftment. Methotrexate a standard immune suppression medication which is given IV on day +1,+3,+6, and +11 post-transplant. Blood draws on days -4,-1,+3,+7,+14 to measure ATG levels.
Location
- University of Alabama at BirminghamBirmingham, Alabama