Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes
Condition: Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia; Myelodysplastic Syndrome
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Syndrome
Intervention: Cyclophosphamide; Cyclosporine; Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion; Fludarabine Phosphate; Mycophenolate Mofetil; Thiotepa; Total-Body Irradiation; Umbilical Cord Blood Transplantation
Intervention description: Given IV; Given IV or PO; Given IV; Given IV; Given IV or PO; Given IV; Undergo high dose or middle intensity TBI; Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Thiotepa; Fludarabine; Fludarabine phosphate; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 163.0
Sex: All
Minimum age: 6 Months
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well donor umbilical cord blood transplant with or
      without ex-vivo expanded cord blood progenitor cells works in treating patients with acute
      myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or
      myelodysplastic syndromes. Giving chemotherapy and total-body irradiation before a donor
      umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the
      patient's immune system from rejecting the donor's cells. When the healthy stem cells and
      ex-vivo expanded cord blood progenitor cells are infused into the patient they may help the
      patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It
      is not yet known whether giving donor umbilical cord blood transplant plus ex-vivo expanded
      cord blood progenitor cells is more effective than giving a donor umbilical cord blood
      transplant alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age criteria:

               -  High dose TBI regimen: 6 months to =< 45 years

               -  Middle intensity TBI regimen: 6 months to =< 65 years

               -  Conditioning regimen selection should be based on the underlying disease,
                  presence of minimal residual disease (MRD), age, co-morbidities, attending
                  physician, and site preference; conditioning regimen will not require
                  stratification of the randomization due to heterogeneity in the cohort of
                  eligible patients.

          -  Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage
             leukemia

               -  All patients must have acute myeloid leukemia (AML) that is considered best
                  treated by stem cell transplant by the referring physician and the attending
                  transplant physician

               -  All patients must be in complete remission (CR) as defined by < 5% blasts by
                  morphology/flow cytometry in a representative bone marrow sample with cellularity
                  >= 15% for age

               -  Patients in which adequate marrow/biopsy specimens cannot be obtained to
                  determine remission status by morphologic assessment, but have fulfilled criteria
                  of remission by flow cytometry, recovery of peripheral blood counts with no
                  circulating blasts, and/or normal cytogenetics (if applicable) may still be
                  eligible; reasonable attempts must be made to obtain an adequate specimen for
                  morphologic assessment, including possible repeat procedures; these patients must
                  be discussed with the principal investigator prior to enrollment

          -  Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage
             leukemia

               -  High risk first complete remission (CR1) (for example, but not limited to:
                  t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia [MLL] rearrangements,
                  hypodiploid); or high risk (HR) as defined by referring institution treatment
                  protocol greater than 1 cycle to obtain CR; second complete remission (CR2) or
                  greater

               -  All patients must be in CR as defined by < 5% blasts by morphology/flow cytometry
                  in a representative bone marrow sample with cellularity >= 15% for age

               -  Patients in which adequate marrow/biopsy specimens cannot be obtained to
                  determine remission status by morphologic assessment, but have fulfilled criteria
                  of remission by flow cytometry, recovery of peripheral blood counts with no
                  circulating blasts, and/or normal cytogenetics (if applicable) may still be
                  eligible; reasonable attempts must be made to obtain an adequate specimen for
                  morphologic assessment, including possible repeat procedures; these patients must
                  be discussed with the principal investigator prior to enrollment

          -  Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in
             first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase
             inhibitor therapy

          -  Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate
             (Int)-2 or high risk (i.e., refractory anemia with excess blasts [RAEB], refractory
             anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe
             pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone
             marrow aspirate morphology

          -  Karnofsky (>= 16 years old) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1

          -  Lansky (< 16 years old) >= 60

          -  Adults: calculated creatinine clearance must be > 60 mL and serum creatinine =< 2
             mg/dL

          -  Children (< 18 years old): calculated creatinine clearance must be > 60 mL/min

          -  Total serum bilirubin must be < 3 mg/dL unless the elevation is thought to be due to
             Gilbert's disease or hemolysis

          -  Transaminases must be < 3 x the upper limit of normal per reference values of
             referring institution

          -  Diffusing capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal

          -  For pediatric patients unable to perform pulmonary function tests, oxygen (O2)
             saturation > 92% on room air

          -  May not be on supplemental oxygen

          -  Left ventricular ejection fraction > 45% OR

          -  Shortening fraction > 26%

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Uncontrolled viral or bacterial infection at the time of study enrollment

          -  Active or recent (prior 6 month) invasive fungal infection without infectious disease
             (ID) consult and approval

          -  History of human immunodeficiency virus (HIV) infection

          -  Pregnant or breastfeeding

          -  Prior myeloablative transplant containing full dose TBI (greater than 8 Gy)

          -  Central nervous system (CNS) leukemic involvement not clearing with intrathecal
             chemotherapy and/or cranial radiation prior to initiation of conditioning; diagnostic
             lumbar puncture is to be performed per protocol

          -  Patients >= 45 years: comorbidity score of 5 or higher