A Myeloablative Conditioning Regimen and Total Body Irradiation Followed by the Transplantation for Patients With Hematological Malignancy
Condition: Cancer; Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma, Non-Hodgkin; Preleukemia; Hematologic Neoplasms; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 2

Summary: 
      In this study two cord blood collections will be used to increase the number of cord blood
      cells you will receive on transplant day. We call this a "double unit" cord blood transplant.
      A previous study suggests double unit cord blood transplant may have a better result. The
      main purpose of this study is to find out how good a cord blood transplant using two cord
      blood collections from two different babies is at curing you of your cancer. Double unit cord
      blood transplants are now being studied as a way to increase the number of cord blood cells
      given to bigger children and adult patients.

      Based on studies that have already been done double unit cord blood transplant appears to be
      safer than if only one cord blood unit is used. However, double unit cord blood transplant is
      a fairly new form of treatment.
    

Detailed description: 
      This is a single arm phase 2 study to obtain a preliminary estimate of efficacy of
      myeloablative double unit umbilical cord blood transplantation (UCBT) as measured by overall
      and disease-free survival at 1 year post transplantation. The UCB graft will consist of two
      (or double) units from two unrelated newborn donors. Patients with hematopoietic malignancy
      at high-risk for relapse or with advanced disease will receive myeloablative conditioning
      with cyclophosphamide (Cy),low dose fludarabine (Flu) and total body irradiation (TBI) with
      post transplantation cyclosporine (CSA) and mycophenolate mofetil (MMF) for GVHD prophylaxis.
    

Intervention name(s): Fludarabine, Cyclophosphamide; Transplantation
Intervention type(s): Drug; Procedure
Intervention description(s): Fludarabine 25 mg/m2/day IV in the morning x 3 days (days -7, -6 and -5) for a total dose of 75 mg/m2 followed by Cyclophosphamide on days -6 and -5. 60mg/kg/day IV over 30-60 minutes x 2 days (days -6 and -5). High volume fluids should commence approximately 12 hours prior to drug and continue until 24 hours after second dose.
Total Body Irradiation: 125 cGy x 11 doses (TID on days -3, -2, -1 and BID on day 0) for a total TBI dose of 1375 cGy. Pediatric patients unable to tolerate a TID dosing schedule can receive 150 cGy x 8 doses (BID on days -3, -2, -1, and 0). All patients will receive GVHD prophylaxis with 2 drugs: Cyclosporine A and Mycophenolate mofetil (MMF).
Units should be given consecutively each over approximately 10-30 minutes.Pre-medication should include acetaminophen and diphenhydramine or hydroxyzine.G-CSF 5 mcg/kg/day IV/SQ (dose rounded to vial size to a maximum of 480 mcg) will be given from day +1 until ANC recovery.; The UCB ( Umbilical Cord Blood) collection known as a unit is processed to remove excess plasma and red cells, tested for sterility, HLA-typed, cryopreserved and stored. This protocol involves the administration of two UCB units from two different donors. The units will be thawed in the Cytotherapy Laboratory as per the current standard operating procedure.
Intervention MeSH terms: Cyclophosphamide; Fludarabine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cancer; Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Total Body Irradiation; Umbilical Cord Blood Grafts; 06-014