Randomized HaploCord Blood Transplantation vs. Double Umbilical Cord Blood Transplantation for Hematologic Malignancies
Condition: Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Acute Lymphocytic Leukemia; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Myeloid; Hematologic Neoplasms; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes
Intervention: CliniMACS® CD34 Reagent System; Fludarabine; Melphalan; Rabbit ATG; Double Umbilical Cord Blood Transplantation; Haplo-Identical Cord Transplantation
Intervention description: If a subject is randomized to the haplo-cord transplant group, their family member will undergo a stem cell collection. The stem cells from the haplo-identical donor will be purified by a procedure called CD34 selection before they are given to the subject. A special device called the CliniMACS® CD34 Reagent System, which is not FDA approved, will be used for this purpose. The manufacturer of the device, Miltenyi Biotec, is providing the researchers access to the device for use in this research study. Because the stem cells from the haplo-identical donor are treated using the CliniMACS CD34 selection device, they cells are considered investigational.; Fludarabine: 30 mg/m2 /day intravenously x 5 days total dose 150 mg/m2. Fludarabine will be dosed according to actual body weight; Melphalan: 70mg/m2/day intravenously x 2 days. Melphalan will be dosed according to actual body weight. Cryotherapy with ice chips will be administered to prevent mucositis.; Rabbit ATG (rATG): 1.5 mg/kg/day intravenously x 4 days, total 6 mg/kg. ATG will be dosed according to actual body weight. The first dose will be infused over at least six hours, and subsequent doses over at least 4 hours. Pre-medications include acetaminophen 650 mg by mouth, diphenhydramine 25-50 mg by mouth or intravenously, and methylprednisolone 2 mg/kg (1 mg/ kg at the initiation and 1 mg/kg half-way through anti-thymocyte globulin administration).; All subjects will receive an UCB dose of > 3 x107/kg nucleated blood cells. It is expected that this will require co-infusion of two UCB in the large majority of cases. If two UCB are required, they will be at least 4/5 matched to the recipient.; If randomized to the haplo-cord group, a family member will undergo a stem cell collection. In both arms, subjects will receive a "conditioning regimen" prior to transplantation. The conditioning regimen utilized in this study incorporates fludarabine-Melphalan and antithymocyte globulin (ATG). This regimen has the advantage of being nearly identical to the regimen utilized for our haplo-cord regimen is based on the experience of the Dana-Farber/Mass-General regimen.
Intervention MeSH terms: Fludarabine; Melphalan; Thymoglobulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Lymphoma

Summary:

      The purpose of this study is compare the efficacy of haplo-cord transplant (investigational
      arm) with that of a more commonly used procedure in which only the cells contained in one or
      two umbilical cords are infused (standard arm).

      We hypothesize that reduced intensity conditioning and haplo-cord transplant results in fast
      engraftment of neutrophils and platelets, low incidences of acute and chronic graft versus
      host disease, low frequency of delayed opportunistic infections, reduced transfusion
      requirements, shortened length of hospital stay and promising long term outcomes. We also
      hypothesize that umbilical cord blood selection can prioritize matching and better matched
      donors can be identified rapidly for most subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject must have a histologically or cytologically confirmed diagnosis of: Acute
             Myelogenous Leukemia Myelodysplastic Syndrome Acute Lymphocytic Leukemia Lymphoma
             (Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma)

          2. Must be > 18 years of age

          3. Subject is likely to benefit from allogeneic transplant in the opinion of the
             transplant physician

          4. An human leukocyte antigen (HLA)-identical related or unrelated donor cannot be
             identified within an appropriate time frame

          5. Karnofsky Performance Status (KPS) of > 80

          6. Subject has acceptable organ and marrow function as defined below: Serum bilirubin <
             2.0mg/dL ALT(SGPT) 3 X upper limit of normal Creatinine Clearance > 50 mL/min as
             estimated by the modified MDRD equation.18

          7. Ability to understand and the willingness to sign a written informed consent document.

          8. A preliminary search has identified both:

               1. Appropriate umbilical cords for a single, or if necessary a double umbilical cord
                  blood (UCB) transplant AND

               2. An appropriate single UCB as well as an appropriate haplo donor for haplo-cord
                  transplant

        Exclusion Criteria:

          1. Myeloproliferative disorders, hemoglobinopathies, severe aplastic anemia or any
             diagnosis not listed under 3.1.1

          2. Life expectancy is severely limited by concomitant illness or uncontrolled infection

          3. Subjects with severely decreased Left Ventricular Ejection Fraction (LVEF) or impaired
             pulmonary function tests (PFTs)

          4. Subject has evidence of chronic active hepatitis or cirrhosis

          5. Subject is HIV-positive

          6. Subject is pregnant or lactating. -