Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
Condition: Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Myelodysplastic Syndrome; Natural Killer Cell Lymphoblastic Leukemia/Lymphoma
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Single Umbilical Cord Blood Unit Transplant; Double Umbilical Cord Blood Unit Transplant; Total Body Irradiation; Cyclophosphamide; Fludarabine; Cyclosporine A; Mycophenolate Mofetil
Intervention type(s): Biological; Biological; Radiation; Drug; Drug; Drug; Drug
Intervention description(s): Unrelated donor, single umbilical cord blood unit; conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF; Unrelated donor, double umbilical cord blood unit; Conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF; 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.; 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.; 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.; 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.; 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.
Other intervention name(s): TBI; Cytoxan®; Fludara; CSA; MMF, Cellcept®
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Cyclosporins
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Double cord blood