Total Body Irradiation With Fludarabine Followed by Combined Umbilical Cord Blood (UCB) Transplants
Condition: Lymphoma; Myeloma; Leukemia; Myelodysplasia; Solid Tumors; Hodgkin's Disease; Myelofibrosis
MeSH terms: Hodgkin Disease; Preleukemia; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 1

Summary: 
      Results to date of umbilical cord blood transplantation in adult and fully mature adolescent
      patients are inferior to what is seen in children, due to a lower stem cell dosage in adults
      and a more toxic conditioning regimen. This phase 1 protocol will use a potentially less
      toxic bone marrow conditioning regimen, followed by infusion of a combined umbilical cord
      blood graft that will provide the patient with a higher stem cell dose than can be given with
      a single umbilical cord blood infusion. The subjects will be conditioned with a total body
      irradiation (TBI) 13.5 Gy and fludarabine. Following conditioning, up to two unrelated,
      partially matched umbilical cord blood grafts will be infused that will provide a minimum
      nucleated cell dose of 3 x 10e7/kg . The primary objective of this study is to measure the
      frequency of treatment-related toxicity and engraftment.
    

Detailed description: 
      Results to date of umbilical cord blood transplantation in adult and fully mature adolescent
      patients are inferior to what is seen in children. There are two reasons for this. First is
      that the stem cell dose, measured in nucleated cells/kg body weight, is considerably lower
      due to the size of the recipient. This results in a higher incidence of graft failure,
      delayed engraftment, and impaired immune reconstitution. Multiple studies have suggested that
      a nucleated cell dose below 1.5 to 2 x 107/kg results in an unacceptably high risk for graft
      failure. Only a minority of adult patients will have a suitably matched umbilical cord blood
      unit that contains more than 1.5 x 107 nucleated cells/kg. The second reason for inferior
      outcome of umbilical cord blood transplantation in adult patients is that in comparison to
      children, the conventional myeloablative bone marrow conditioning regimens are more toxic.
      This phase 1 protocol will use a potentially less toxic bone marrow conditioning regimen,
      followed by infusion of a combined umbilical cord blood graft that will provide the patient
      with a higher stem cell dose than can be given with a single umbilical cord blood infusion.
      The subjects will be conditioned with a TBI 13.5 Gy and fludarabine. Fludarabine
      pharmacokinetics will be measured and correlated with the kinetics of donor cell engraftment
      as well frequency of treatment-related toxicity. Following conditioning, up to two unrelated,
      partially matched umbilical cord blood grafts will be infused that will provide a minimum
      nucleated cell dose of 3 x 10e7/kg. The primary objective of this study is to measure the
      frequency of treatment-related toxicity and engraftment.
    

Intervention name(s): Total Body Irradiation with Fludarabine in UCB Transplants
Intervention type(s): Procedure
Intervention description(s): Administration of the preparative regimen, infusion of the stem cell graft, inpatient care during the immediate post-transplant period and outpatient follow-up for the first 3 months after transplant and at 6, 12, 24 and 36 months. Patients will have human leukocyte antigen (HLA) serologic typing and DNA typing. Bags of UCB are thawed, and diluted by 1:1 volume using a 5% albumin/dextran solution. The thawed and diluted umbilical cord blood unit (UCBU) is next weighed and centrifuged. Specimens are obtained for cell count and viability, culture, clonogenic assays, and phenotype. The UCB is infused at a rate of 1-3 ml/min. Furosemide (0.5-1.0 mg/kg/dose) may be given if volume overload or decreased urine output occurs. Each UCB infusion shall be tested for sterility, CFU content, number of CD34+ cells, cell count and viability.
Intervention MeSH terms: Fludarabine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Umbilical Cord Blood Graft; Stem Cell Transplantation