Expanded Umbilical Cord Blood Product HSC835 in Treating Patients with Hematological Malignancies

Inclusion Criteria

• Adult patients must have a hematological malignancy, as described below: * Acute leukemias: ** Acute lymphoblastic leukemia (ALL) in first complete remission (CR1) that is NOT considered favorable-risk as defined by the presence of at least one of the following: *** Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), other mixed lineage leukemia (MLL) rearrangements *** White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis, *** Recipient age older than 30 years at diagnosis, *** Time to CR greater than 4 weeks ** Acute myelogeneous leukemia (AML) in first complete remission (CR1) that is NOT considered as favorable-risk; favorable risk is defined as having one of the following: *** t(8,21) without CKIT mutation *** inv(16) without CKIT mutation or t(16;16) *** Normal karyotype with mutated nucleophosmin (NPM1) and not FLT-IND *** Normal karyotype with double mutated CCAAT/enhancer binding protein alpha (CEBPA) *** Acute promyelocytic leukemia (APL) in first molecular remission at end of consolidation ** Acute leukemias in second (2nd) or subsequent ** Biphenotypic/undifferentiated/prolymphocytic leukemias in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR * Chronic myelogenous leukemia (CML) excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate * Myelodysplastic syndrome (MDS): International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% * Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), marginal zone B-cell lymphoma or follicular lymphoma that have progressed after at least two prior therapies; patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant * Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or first or greater partial remission (PR1+) * Large cell non-Hodgkin lymphoma (NHL) > CR2/> PR2; patients in CR2/PR2 with initial short remission (< 6 months) are eligible * Lymphoblastic lymphoma, Burkitt lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year * Multiple myeloma beyond PR2; patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy * Natural killer (NK) cell leukemia
• Pediatric patients must have a hematological malignancy as described below: * AML: high risk CR1 (preceding MDS, intermediate to high risk cytogenetics, >= 2 cycles to obtain CR, French-American-British classification system [FAB] M6); CR2+, first relapse with < 25% blasts in bone marrow; morphologic complete remission with incomplete blood count recovery; therapy-related AML for which prior malignancy has been in remission for at least 12 months * ALL: high risk CR1 (Philadelphia chromosome positive [Ph+] ALL, MLL rearrangements with slow early response, hypodiploidy, end of induction M3 bone marrow, end of induction M2 with M2-3 at day 42, evidence of minimal residual disease [MRD]); high risk CR2 (Ph+ALL, bone marrow relapse < 36 months from induction, T-lineage relapse at any time, very early isolated central nervous system (CNS) relapse, slow induction after relapse at any time, evidence of MRD); >= CR3 * NK cell lymphoblastic leukemia in any CR * Biphenotypic or undifferentiated leukemia in any CR or if in first relapse must have less than 25% blasts in bone marrow * Myelodysplastic syndrome (MDS) at any stage * Chronic myelogenous leukemia (CML) in chronic or accelerated phase Evidence of CNS leukemia must be treated and in CNS CR to be eligible for the study
• Karnofsky score >= 80% (adults), Lansky score >= 50% (pediatrics)
• Creatinine < 2.0 mg/dL
• Bilirubin < 3 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x ULN
• Alkaline phosphatase (ALP) < 3 x ULN
• Corrected diffusion capacity of the lung for carbon monoxide (DLCOcorr) > 50% ULN
• Left ventricular ejection fraction >= 45%
• The unrelated UCB donors must be 4-6/6 human leukocyte antigen (HLA)-A, B, DRB1 matched with the recipient (HLA matching using molecular techniques: A and B at antigen level and DRB1 at allele level) and the UCB units must come from (a) qualified UCB bank(s) according to institutional standard operating procedures (SOPs); if the UCB unit is "unlicensed" (most commonly on the basis of location [e.g., European countries], testing by non-Clinical Laboratory Improvements Amendment (CLIA) approved laboratories, or the UCB was collected before May 25, 2005), the Sponsor will make the final decision on patient eligibility based on the reason why the UCB is unlicensed * The patient must be free of HLA-specific antibodies for HLA antigens present on matched grafts * Suitable UCB units or haplo-identical donor available according to the UCB graft selection algorithm

Exclusion Criteria

• Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
• History of human immunodeficiency virus (HIV) infection
• Pregnant or breast feeding; all females of childbearing potential must have a blood or urine pregnancy test within 2 weeks prior to enrollment to rule out pregnancy
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception from the day of transplant and for one week after infusion; high effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment * Male sterilization (at least 6 months prior to screening); for female subjects on the study, the vasectomized male partner should be the sole partner for that subject * Combination of any two of the following (a+b or a+c, or b+c) ** a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception ** b. Placement of an intrauterine device (IUD) or intrauterine system (IUS) ** c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository * In case of use of oral contraception women should have been stabile on the same pill for a minimum of 3 months before taking study treatment
• Male patients unless they are using condoms as contraception starting on the day of transplantation up until one week after infusion
• Prior myeloablative allotransplant
• Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation as per the assessment of the radiation oncologist
• Patients who have received yttrium (Y)-90 ibritumomab (Zevalin) or iodine (I)-131 tositumomab (Bexxar), as part of their salvage therapy are not eligible for myeloablative UCB transplant