Clinical trial NCT00801931
Conditions: Leukemia Lymphoma Neuroblastoma Immunodeficiencies Anemia
Keywords: Cord Blood Transplant Allogeneic Stem Cell Transplant
Sponsor: Columbia University
Start date: 2007-09-06; Completion date: 2009-05-05
Enrollment: 1 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the safety and toxicity and feasibility of double umbilical cord blood transplantation (DUCBT) in patients with selected malignant and non-malignant, and to quantify the percentage and donor sources of mixed donor chimerism following DUCBT in patients with selected malignant and non-malignant disorders.

Detailed description:
Allogeneic stem cell transplantation from an human leukocyte antigen (HLA) matched related family donor is the treatment of choice for a wide variety of malignant and non-malignant disorders. Unfortunately, only 25% of potential recipients have an HLA matched related family donor, leaving approximately 75% of potential recipients requiring alternative sources of HLA matched allogeneic stem cells. One potential source of HLA matched allogeneic stem cells is from unrelated adult donors that have been identified in the national and international donor registries. However, several limitations restrict the uniform utilization of unrelated allogeneic adult donors including ethnic background of the recipient, acuity and timing of planned allogeneic transplant, availability of donor, and high risk of severe acute graft-versus-host disease (GVHD) (III/IV), among others. The investigators have recently identified a new alternative source of allogeneic stem cells, unrelated cryopreserved placental/cord blood stem cells.

Arms: arm 1: Patients will start their pre-conditioning regimen on Day -8. Fractionated total body irradiation (TBI) will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5 and-4, Cyclophosphamide on Days -3 and -2 and- rabbit antithymocyte globulin on Days -4, -3, -2 and -1.The double cord blood infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/mycophenolate mofetil (MMF). arm 2: Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with double cord blood infusion on Day 0. Granulocyte-macrophage colony-stimulating factor (GM-CSF) hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF. arm 3: Patients will start their GVHD prophylaxis with Tacrolimus on Day -8. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF. arm 4: Patients will start their GVHD prophylaxis with Tacrolimus on Day -6. Patients will receive busulfan twice daily on Days -6, and-5; fludarabine on Days -6, -5, -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF. arm 5: Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and horse antithymocyte globulin on Days -5, -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF. arm 6: Patients will begin fosphenytoin or phenytoin prophylaxis on Day -10. Patients will receive busulfan on days -9, -8, -7 and -6, cyclophosphamide on days -5, -4, -3, and -2 and rabbit antithymocyte globulin on days -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
Interventions: intervention 1: Alemtuzumab intervention 2: Total Body Irradiation intervention 3: Melphalan intervention 4: Busulfan intervention 5: Phenytoin intervention 6: Fludarabine intervention 7: Cyclophosphamide intervention 8: Horse Antithymocyte Globulin intervention 9: Rabbit Antithymocyte Globulin intervention 10: Thiotepa
Intervention descriptions: intervention 1: Each dose of alemtuzumab is to be diluted in 5% dextrose in water (D5W) or normal saling (NS) (maximum concentration: 0.3 mg/mL) for intravenous (IV) infusion over two hours. intervention 2: None intervention 3: Melphalan 45mg/m2 (1.5 mg/kg IV for children \<1 year of age or \<10 kg) diluted in 0.9% NS to a concentration of 0.1- 0.45mg/ml, given IV over 30 minutes. intervention 4: (Busulfex) will be given IV in 0.9% sodium chloride or D5W to a final solution for infusion equal to 10 times the volume of diluent to Busulfex (to a concentration \>0.5 mg/mL), through a central venous access device over 2 hours. intervention 5: Fosphenytoin can be administered in D5W or 0.9% sodium chloride to a final concentration ranging from 1.5 to 25 mg PE/ml at a rate of 1-3 mg phenytoin sodium equivalents (PE)/kg/min up to 50-150 mg PE/minute. intervention 6: Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes. intervention 7: Cyclophosphamide should be infused over one hour. The drug can be diluted in D5W, NS, or other solutions (100-250 mL) to a maximum concentration of 20 mg/mL. intervention 8: Horse Antithymocyte Globulin (ATG \[horse\]) will be diluted in 0.9% sodium chloride or 0.45% sodium chloride for IV infusion (through an inline filter with pore size of 0.2 micrometer) to a concentration of 1-4 mg/ml and infused through a central venous catheter over 8 hours in Regimen E. intervention 9: Rabbit Anti-Thymocyte Globulin (rabbit ATG) will be diluted in 0.9% sodium chloride or D5W for IV infusion (through an in-line filter with pore size of 0.22 micrometer) to a concentration of 0.5 mg/ml and infused through a central venous catheter over 8 hours for all doses on Days -4, -3, -2, and -1 in Regimens A, B, D and F. intervention 10: Thiotepa should be diluted in NS (1-5 mg/ml) and infused over 2 hrs on Days -8, -4. IV fluids should be at maintenance rate (1500 ml/m2).

Protocol documents: