Standard-of-Care Reduced-Intensity Conditioning (RIC) With 200 Versus 400 cGy of Total Body Irradiation (TBI) in Patients With Acute Leukemia Undergoing First Allogeneic Blood or Marrow Transplantation (BMT)

This is a randomized phase II trial of standard-of-care reduced-intensity conditioning (RIC) with 200 versus 400 cGy of total body irradiation (TBI) in patients with acute leukemia undergoing first allogeneic blood or marrow Transplantation (BMT). The primary objective is to compare the rates of graft-versus-host disease-free and relapse-free survival (GRFS) between patients in the two cohorts.

This research is being done to learn more about reduced-intensity conditioning stem cell transplant for patients with acute leukemias or acute lymphoblastic lymphoma, using stem cell donation from the peripheral blood or bone marrow from a relative or an unrelated donor. The purpose of this study is to determine if a TBI dose of 400 cGy yields better transplant-related outcomes than a TBI dose of 200 cGy when leukemia patients in remission undergo a reduced-intensity conditioning transplant using high-dose post-transplantation cyclophosphamide as GVHD prophylaxis. The study will use graft-versus-host disease-free, relapse-free survival (GRFS) as its primary endpoint. GRFS will be defined as time from transplant to the first of any grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, disease relapse or progression, or death by any cause. The transplantation of stem cells from the peripheral blood or bone marrow of a related or unrelated donor is a standard, established treatment for both acute leukemias and acute lymphoblastic lymphoma. Possible donors include parents, siblings, and children. The donor may also be unrelated to the patient. In order to help the donor cells grow, standard of care chemotherapy and radiation will be given before the transplant. Standard of care prophylactic immunosuppression will be used and includes the use of post-transplant cyclophosphamide. These medications lower the risk of GVHD and graft rejection. The exact planned duration of prophylactic immunosuppression will be dictated by institutional protocols based on donor type. Reduced-intensity transplants have been given to many people in the treatment of various cancers. Over 1000 people at Johns Hopkins have received this type of transplant. Standard chemotherapy, commonly fludarabine and cyclophosphamide, along with radiation will be administered before infusion of the cells transplanted from the donor. The radiation administered as part of this pre-transplant conditioning regimen is called total body irradiation (TBI). This is important in allowing the donated stem cells to grow. TBI may also kill residual cancer cells. The optimal dose of TBI is unknown. Very high doses of TBI have been used previously and are associated with some anti-cancer activity but also significant side effects and an increased risk of death. Due to the significant risks associated with high doses of TBI, the practice at Johns Hopkins has been to use lower doses of TBI, either 200 or 400 centiGray (cGy) in one administration. It is unclear which of these doses, 200 or 400 centiGray (cGy), is superior in balancing anti-cancer effects and reducing side effects. The higher dose of TBI may increase the anti-cancer activity and the chance of engraftment, thereby reducing the patient's risk of disease relapse, which can be fatal. The lower dose of TBI may decrease the risk of blood transfusions, infertility, infections, GVHD, second cancers, and death without disease relapse. The main goal of the study is to see which of these doses of TBI, 200 or 400 cGy, as part of reduced-intensity conditioning before stem cell transplantation, is superior in terms of reducing the combined risk of leukemia relapse, death, and severe GVHD. The study also looks at whether there is a difference in whether the donated stem cells engraft, time to blood count recovery, time admitted to a hospital, new cancers developing after stem cell transplant, overall severe side effects, how many people survive without cancer, and how many people survive overall depending on the dose of radiation received. Patients will be randomly assigned to receive either 200 or 400 cGy of total body irradiation (TBI) as part of the reduced intensity conditioning regimen before stem cell transplant. This decision will be based a computer system that randomizes people into each group. The study regimen includes several days of chemotherapy, immunosuppressant, and a single dose of radiation, either 200 or 400 cGy, followed by the bone marrow transplant. After the transplant, patients will receive two doses of the intravenous chemotherapy cyclophosphamide and two oral medications to prevent graft versus host disease and to aid in bone marrow engraftment. Participation on this study will last up to 2 years after transplant.