Reduced Intensity Transplant Using Extracorporeal Photopheresis
Recruitment status was: Recruiting
Stem cell transplantation may be used to cure childhood cancers, and other diseases. Traditionally, stem cell transplants use high doses of chemotherapy and radiation. This regimen may cause significant problems after transplant such as infertility, infection, and graft versus host disease (GVHD).
Reduced intensity transplant (RIT) uses medications which weaken the immune system, allowing donor cells to take over. The goal of a RIT is to reduce the risk for complications after transplant. Usually medication is used to weaken the immune system, but there are other options such as extracorporeal photopheresis (ECP) that may be less toxic.
ECP is currently used for the treatment of GVHD and certain lymphomas. ECP uses a machine that filters white blood cells from the blood, treats them with ultraviolet (UV) light, and then gives all the cells back to the patient. The patient's immune system becomes weaker, allowing the donor cells to replace those of the patient. Studies involving the use of ECP for conditioning have shown fewer side effects than the use of medications.
The primary purpose of this clinical research trial is to evaluate the safety and feasibility of ECP as part of a preparative regimen for RIT in children and young adults.
Procedure: Extracorporeal Photopheresis
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Reduced Intensity Stem Cell Transplant in Children and Young Adults Utilizing Photopheresis, Fludarabine, and Busulfan|
- To determine the feasibility of using photopheresis as the backbone of a reduced intensity transplant regimen to reduce transplant related mortality and acute and chronic graft versus host disease (GVHD) [ Time Frame: Throughout Treatment ] [ Designated as safety issue: Yes ]
- To determine time to engraftment and the percentage of patients achieving full engraftment by day +100. Engraftment will be defined as > 95% total donor chimerism as determined by restriction fragment length polymorphism (RFLP). [ Time Frame: By Day +100 ] [ Designated as safety issue: Yes ]
- To determine the rate of grades III and IV acute GVHD. [ Time Frame: Throughout Treatment ] [ Designated as safety issue: Yes ]
- To evaluate 100 day transplant related mortality [ Time Frame: Through Day +100 ] [ Designated as safety issue: Yes ]
- To establish patterns of biological effects of photopheresis on dendritic cell and CD4/CD8 populations, CD4/CD25 populations, IFN-gamma, TNF-alpha, IL-10, IL-12, and IL-4 [ Time Frame: Pre Transplant through 1 year post stem cell transplant ] [ Designated as safety issue: No ]
|Study Start Date:||July 2005|
|Estimated Study Completion Date:||January 2010|
|Estimated Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Procedure: Extracorporeal Photopheresis
This study tests the feasibility of a reduced intensity preparative regimen for stem cell transplant including extracorporeal photopheresis (ECP), busulfan, and fludarabine in patients with leukemia, lymphoma, and certain non-malignant diseases. The current reduced intensity protocol includes busulfan, fludarabine, and anti-thymocyte immunoglobulin. ECP is currently used in diseases such as chronic GVHD and cutaneous T cell lymphoma. The mechanism of ECP has not been defined. It is hypothesized that exposure of white blood cells to ultraviolet light with 8-methoxypsoralen initiates an apoptotic cellular cascade. Apoptotic cells are recognized and removed by the reticuloendothelial system, initiating the secretion of anti-inflammatory cytokines and the reduction of proinflammatory cytokines. Antigen presenting cells then regulate immune responses through the induction of tolerance.
Here we incorporate the use of ECP, fludarabine, and busulfan in the preparative regimen, followed by ECP as prophylaxis for acute graft versus host disease. We hypothesize that photopheresis is safe and feasible, and patients will have similar rates of engraftment with less GVHD as those treated with current reduced intensity protocols. The use of ECP prior to transplant provides immunosuppression promoting host engraftment. Furthermore, the introduction of ECP following transplant may be able to induce tolerance thereby reducing rates of GVHD.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00179790
|United States, Illinois|
|Children's Memorial Hospital|
|Chicago, Illinois, United States, 60614|
|Principal Investigator:||Jennifer Schneiderman, MD, MS||Ann & Robert H Lurie Children's Hospital of Chicago|