GC P#05.01.020, A Multicenter, Randomized, Phase III Registration Trial of Transplantation of NiCord®, Ex Vivo Expanded, Umbilical Cord Blood-derived, Stem and Progenitor Cells, versus Unmanipulated Umbilical Cord Blood for Patients with Hematological Malignancies

1. Patients must be 12-65 years of age at the time of randomization 2. Patients with one of the following hematological malignancies: Acute lymphoblastic leukemia (ALL) at one of the following stages: a. High risk first complete morphologic remission (CR1), defined as one or more of the following: - -- The presence of adverse cytogenetics or adverse molecular changes. Examples of adverse cytogenetics are t(4;11), t(9;22), t(1;19), MLL rearrangements t(11q23) or severe hypodiploid ALL - -- Extreme leukocytosis at diagnosis (WBC >30,000/[MICRO-SYMBOL]l for B-ALL or >100,000/[MICRO-SYMBOL]l for T-ALL) - -- Failure to achieve complete morphologic remission after first induction therapy - -- Evidence of minimal residual disease (MRD) at screening by flow cytometry or molecular testing - -- Slow response to induction therapy, as evidenced by peripheral blood leukemic blasts one week after start of induction, or >10% leukemic blasts in bone marrow 2 weeks after start of induction - -- Age older than 30 years at diagnosis b. Second or subsequent remission Acute myelogenous leukemia (AML) at one of the following stages: a. First complete morphologic remission (CR1) that is NOT considered as favorable-risk Favorable risk is defined as having one or more of the following at diagnosis and absence of MRD at screening: - -- t(8,21) without cKIT mutation - -- inv(16) or t(16;16) without cKIT mutation - -- Normal karyotype with mutated NPM1 and no FLT-3 Internal Tandem Duplication - -- Normal karyotype with double mutated CEBPA - -- APL in first or second molecular remission at end of consolidation b. Patients in CR1 with one or more of the favorable risk criteria but with additional high risk features may be considered eligible upon consultation with the study chairs. c. Second or subsequent remission Chronic myelogenous leukemia (CML) at one of the following phases: a. Chronic phase with one or more of the following characteristics: - -- Failure to achieve a primary hematologic or cytogenetic response to either nilotinib or dasatinib (following European LeukemiaNet timelines summarized in Appendix H) - -- Intolerance to/failure of two tyrosine kinase inhibitors (TKI) - -- Any T315I mutation - -- Prior blast crisis b. Accelerated phase with one or more of the following characteristics: - -- Newly diagnosed patients who do not achieve an optimal response to TKIs as outlined in the European LeukemiaNet timelines summarized in Appendix H - -- TKI-treated patients who progress from chronic phase c. Prior blast crisis (myeloid or lymphoid) currently in chronic phase or in complete morphologic or molecular remission Myelodysplastic Syndrome (MDS) with history of one or more of the following: o International Prognostic Scoring System (IPSS) risk category of INT-1 or greater. MDS patients categorized as INT-1 on primary presentation must have life threatening neutropenia (ANC < 0.5x109/L) or thrombocytopenia (platelets < 30x109/L). o Revised International Prognostic Scoring System (IPPS-R) risk category of intermediate or greater Biphenotypic/undifferentiated/Prolymphocytic/Dendritic Cell Leukemias and Natural Killer Cell Malignancies in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR o Lymphoma, meeting one of more of the following criteria: Burkitt[Single Quote]s lymphoma in second or subsequent CR OR o High risk lymphomas in first CR, including, enteropathy-associated T cell lymphoma, or hepatosplenic gammadelta T cell lymphoma OR o Chemotherapy-sensitive (defined as at least stable disease) lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are ineligible for an autologous transplant. (Patients with CLL are not eligible regardless of disease status) 3. CBU criteria as described above. 4. Patients who will be starting conditioning prior to NiCord release for infusion (i.e., NiCord arrival on site in adequate condition) must have an additional partially HLA-matched CBU, reserved as a backup to the NiCord arm in case of production failure. The backup CBU must be HLA-matched at 4-6/6 HLA class I (HLA-A & HLA-B, low resolution) and II (HLA-DRB1, high resolution) loci with the patient. A second backup CBU is recommended to be added in the below cases: * - If the back-up CBU is HLA-matched at 5 or 6/6and contains a pre-cryopreserved (post processing) total nucleated cell dose of <2.5x107 TNC/kg, OR a pre-cryopreserved (post processing) CD34+ cell dose of <1.2 x105 CD34+ cells/kg * - If the back-up CBU is HLA-matched at 4/6and contains a pre-cryopreserved (post processing) total nucleated cell dose of <3.5x107 TNC/kg, OR a pre-cryopreserved (post processing) CD34+ cell dose of <1.7 x105 CD34+ cells/kg In case of two back-up CBUs, the second back-up CBU must be HLA-matched at 4-6/6 HLA class I (HLA-A & HLA-B, low resolution) and II (HLA-DRB1, high resolution) loci with the patient. The back-up CBUs are recommended to have a combined pre-cryopreserved (post processing) total nucleated cell dose of at least 3x107 TNC/kg. 5. Patient[Single Quote]s Performance score >=70% by Karnofsky or Lansky 6. Patient has sufficient physiologic reserves including: a. Cardiac: Left ventricular ejection fraction (LVEF) of >=40% by echocardiogram, radionuclide scan or cardiac MRI b. Pulmonary function tests (prior to treatment with bronchodilators) demonstrating FVC and FEV1 of >50% of predicted for age and cDLCO > 50% of predicted (If PFT testing included the use of bronchodilators, then the baseline results during testing prior to the administration of any medications should be used when determining eligibility). c. Renal: Creatinine clearance test (by Cockcroft-Gault equation) >=60 mL/min d. Hepatic: Serum Bilirubin < 2.0 mg/dl; Hepatic transaminases (ALT and AST) < 3 x upper limit of normal range 7. Females of childbearing potential, defined as any female who has experienced menarche and is not postmenopausal (defined as not having a menstrual period for at least 24 months) or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy), agree to use an appropriate method of contraception from at least 7 days prior to conditioning regimen therapy until completion of follow-up procedures. An appropriate method of contraception is defined as one that results in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner. 8. Patient (or legal guardian) signs the written informed consent after being aware of the nature of the patient[Single Quote]s disease and willingly consents to the treatment program after being informed of alternative treatments, potential risks, benefits, and discomforts. Pregnant Partners: -A female pregnant partner of a male study subject. This pregnant partner must have become pregnant during the study