Trials / Completed

CompletedNCT00412360

Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)

Multi-center, Open Label, Randomized Trial Comparing Single Versus Double Umbilical Cord Blood (UCB) Transplantation in Pediatric Patients With High Risk Leukemia and Myelodysplasia (BMT CTN #0501)

Status: Completed
Phase: Phase 3
Study type: Interventional
Enrollment: 224 (actual)

Sponsor: Medical College of Wisconsin · Academic / Other
Sex: All
Age: 1 Year – 21 Years
Healthy volunteers: Not accepted

Summary

This study is a Phase III, randomized, open-label, multi-center, prospective study of single umbilical cord blood (UCB) transplantation versus double UCB transplantation in pediatric patients with hematologic malignancies.

Detailed description

BACKGROUND: In nearly every large single center or registry analysis of outcomes after UCB transplantation, cell dose is identified as an important factor influencing the incidence and rate of hematopoietic recovery, risk of transplant-related mortality, and probability of survival. Pilot data suggest that infusion of two partially human leukocyte antigen (HLA)-matched UCB units, which always augments the graft cell dose, is safe and may improve neutrophil recovery and survival. To determine whether the infusion of two UCB units enhances survival, a multi-center, open-label, randomized trial is proposed. As adequate single UCB units can be identified for more than 80% of pediatric recipients (in contrast to less than 30% for adults), this study will be open only to pediatric patients. The population will be restricted to patients with high-risk hematologic malignancy, the most common indication of UCB transplantation in children. DESIGN NARRATIVE: Participants will include patients 1 to 21 years of age with a diagnosis of hematological malignancy and with two partially HLA-matched UCB units. Units must be HLA-matched at 3 of 6 HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution molecular typing) with each other and 4 of 6 with the recipient. Two appropriately HLA-matched units must be available such that one unit delivers a pre-cryopreserved, nucleated cell dose of at least 2.5 x 10\^7 per kilogram and the second unit delivers at least 1.5 x 10\^7 per kilogram. Patients will be randomized no more than 14 days prior to initiation of conditioning. UCB units will be shipped prior to initiation of conditioning. The preparative regimen will consist of the following: * Fludarabine: 25 mg/m2/day IV on Days -10, -9, and -8. * Total Body Irradiation (TBI): 165 cGy twice daily on Days -7, -6, -5, and -4. * Cyclophosphamide: 60 mg/kg/day x 2 on Days -3 and -2. * Day 0 will be the day of the UCB transplant. The Graft-vs-Host-Disease (GVHD) prophylaxis regimen will be mycophenolate mofetil (MMF) 15 mg/kg IV BID on Day -3 to Day + 45 and cyclosporine A (CSA) to maintain level 200-400 ng/mL beginning on Day -3. Patients will be followed for at least 24 months post-transplant.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Single Umbilical Cord Blood Unit Transplant	Unrelated donor, single umbilical cord blood unit; conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF
BIOLOGICAL	Double Umbilical Cord Blood Unit Transplant	Unrelated donor, double umbilical cord blood unit; Conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF
RADIATION	Total Body Irradiation	The TBI will be delivered from either a linear accelerator or cobalt source at a dose rate of between 4 and 26 cGy/minute using energies of between 1 and 25 MV.
DRUG	Cyclophosphamide	Cyclophosphamide 60 mg/kg/day will be administered as a 2 hour intravenous infusion with a high volume fluid flush on Days -3 and -2.
DRUG	Fludarabine	Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -10 through -8. Fludarabine will not be dose adjusted for body weight.
DRUG	Cyclosporine A	CSA will be administered beginning on Day -3 and doses will be adjusted to maintain a level of 200-400 ng/mL by TDX method (or 100-250 ng/mL by Tandem MS or equivalent level for other CSA testing methods). CSA can be administered per institutional practice.
DRUG	Mycophenolate Mofetil	MMF will be given at a dose of 1 gram IV q 8 hours if \> 50 kg or 15 mg/kg IV q 8 hours if \< 50 kg beginning the morning of Day -3.

Timeline

Start date: 2006-12-01
Primary completion: 2014-03-01
Completion: 2014-10-01
First posted: 2006-12-18
Last updated: 2021-10-28
Results posted: 2015-12-21

Locations

38 sites across 3 countries: United States, Australia, Canada

Source: ClinicalTrials.gov record NCT00412360. Inclusion in this directory is not an endorsement.