Umbilical Cord Blood Transplant With Added Sugar and Chemotherapy and Radiation Therapy in Treating Patients With Leukemia or Lymphoma
Condition: Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Biphenotypic Leukemia; Acute Leukemia; Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chemotherapy-Related Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Hodgkin Lymphoma; Langerhans Cell Histiocytosis; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Myelodysplastic Syndrome; Small Lymphocytic Lymphoma; Therapy-Related Myelodysplastic Syndrome
MeSH terms: Lymphoma; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Neoplasm, Residual; Leukemia, Myeloid, Accelerated Phase; Leukemia, Biphenotypic, Acute; Histiocytosis, Langerhans-Cell; Myelodysplastic Syndromes; Histiocytosis; Anemia, Refractory, with Excess of Blasts; Syndrome
Intervention: Anti-Thymocyte Globulin; Busulfan; Clofarabine; Cyclophosphamide; Filgrastim-sndz; Fludarabine; Melphalan; Mycophenolate Mofetil; Rituximab; Tacrolimus; Total-Body Irradiation; Umbilical Cord Blood Transplantation
Intervention description: Given IV; Given IV; Given IV; Given IV; Given SC; Given IV; Given IV; Given IV or PO; Given IV; Given IV; Undergo total body irradiation; Undergo cord blood transplant
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Melphalan; Busulfan; Mechlorethamine; Nitrogen Mustard Compounds; Rituximab; Fludarabine; Clofarabine; Antineoplastic Agents, Immunological; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 12 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well an umbilical cord blood transplant with added sugar
      works with chemotherapy and radiation therapy in treating patients with leukemia or lymphoma.
      Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant
      helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem
      cells) and cancer cells. When the healthy stem cells from a donor are infused into the
      patient they may help the patient's bone marrow make stem cells, red blood cells, white blood
      cells, and platelets. The umbilical cord blood cells will be grown ("expanded") on a special
      layer of cells collected from the bone marrow of healthy volunteers in a laboratory. A type
      of sugar will also be added to the cells in the laboratory that may help the transplant to
      "take" faster.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have one of the following hematologic malignancies: a. Acute myelogenous
             leukemia (AML), induction failure, high-risk for relapse first remission (with
             intermediate-risk or high-risk cytogenetics, flt3 mutation positive and/or evidence of
             minimal residual disease by flow cytometry), secondary leukemia from prior
             chemotherapy and/or arising from myelodysplastic syndrome (MDS), Langerhan's cell
             histiocytosis, any disease beyond first remission. b. Myelodysplastic syndrome (MDS):
             MDS International Prognostic Scoring System (IPSS) INT-1 will be enrolled only if the
             subjects have failed previous leukemia treatments and are transfusion-dependent. MDS
             may be primary or therapy related, including patients that will be considered for
             transplant. Including the following categories: 1) Revised IPSS intermediate and high
             risk groups, 2) MDS with transfusion dependency, 3) Failure to respond or progression
             of disease on hypomethylating agents, 4) Refractory anemia with excess of blasts, 5)
             Transformation to acute leukemia, 6) Chronic myelomonocytic leukemia, 7) Atypical
             MDS/myeloproliferative syndromes, 8) Complex karyotype, abn(3g), -5/5g-, -7/7g-,
             abn(12p), abn(17p). c. Acute lymphoblastic leukemia (ALL) patients with the following
             will be considered: induction failure, primary refractory to treatment (do not achieve
             complete remission after first course of therapy) or are beyond first remission
             including second or greater remission or active disease. Patients in first remission
             are eligible if they are considered high risk, defined as any of the following
             detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex
             karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or
             evidence of minimal residual disease, or acute biphenotypic leukemia which excludes >
             7 chromosomal abnormalities, or double hit non-Hodgkin's lymphoma. Non-Hodgkin's
             lymphoma (NHL) in second or third complete remission or relapse (including relapse
             post autologous hematopoietic stem cell transplant), or relapsed double hit lymphoma.
             Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with
             progressive disease with progression after standard of care therapy or have
             failed/been intolerant to ibrutinib. Chronic myelogenous leukemia (CML) second chronic
             phase or accelerated phase. Hodgkin's disease (HD): Induction failure after the first
             complete remission, or relapse (including relapse post autologous hematopoietic stem
             cell transplant), or those with active disease.

          -  The first 6 patients must be >= 18 and =< 65 years old. The subsequent patients may
             include pediatric patients >= 12 and =< 65 years old. Eligibility for pediatric
             patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC)
             pediatrician.

          -  Performance score of at least 80% by Karnofsky or performance score (PS) < 3 (Eastern
             Cooperative Oncology Group [ECOG]) (age >= 12 years)

          -  Left ventricular ejection fraction of > 40%.

          -  Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50%
             predicted.

          -  Creatinine =< 1.5 mg/dL for patients 12 years old and older and =< 1 for patients
             younger than 12 years old.

          -  Serum glutamate pyruvate transaminase (SGPT) =< to 2.0 x normal.

          -  Bilirubin =< to 2.0 x normal.

          -  Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing
             potential defined as not post-menopausal for 12 months or no previous surgical
             sterilization and willing to use an effective contraceptive measure while on study.

          -  Patients must have two cord blood (CB) units available which are matched with the
             patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. Each
             cord must contain at least 1.5 x 10^7 total nucleated cells/Kg recipient body weight
             (pre-thaw).

          -  Have identified a backup cells source in case of engraftment failure. The source can
             be autologous, related or unrelated.

          -  Patient must not have a 10/10 HLA matched family member or unrelated donor.

          -  Patients will have a back-up graft from any of the following: an available fraction of
             autologous marrow; or peripheral blood progenitor cells (PBPCs) harvested and
             cryopreserved; or family member donor; or a third cord blood unit.

          -  Prior to initiating chemotherapy in this study, twenty-one or more days must have
             elapsed since the patient's last radiation or chemotherapy administration (Hydrea,
             Gleevec and other tyrosine kinase inhibitors [TKI] as well as intrathecal therapy are
             accepted exceptions).

        Exclusion Criteria:

          -  Patients with known history of human immunodeficiency virus/acquired immunodeficiency
             syndrome (HIV/AIDS).

          -  Patients with positive hepatitis serology that is definitive of active disease.

          -  Active central nervous system (CNS) disease in patient with history of CNS malignancy.

          -  Patients with chronic active hepatitis or cirrhosis. If positive hepatitis serology,
             the study chair may deem the patient eligible based on the results of liver biopsy.

          -  Patients with uncontrolled serious medical condition such as persistent septicemia
             despite adequate antibiotic therapy, decompensated congestive heart failure despite
             cardiac medications or pulmonary insufficiency requiring intubation (excluding primary
             disease for which CB transplantation is proposed), or psychiatric condition that would
             limit informed consent.

          -  Positive beta HCG in female of child-bearing potential defined as not post-menopausal
             for 12 months or no previous surgical sterilization or breast-feeding.

          -  Pediatric patients with acute lymphoblastic leukemia (ALL) that is t (9,22) positive
             in first remission are not eligible unless there is evidence of minimal residual
             disease after initial induction and/or consolidation treatment or the pediatric
             Philadelphia chromosome positive (Ph+) ALL is clinically refractory to available
             therapies with evidence of persistence in the bone marrow or peripheral blood.

          -  Patients with options for treatment that are known to be curative are not eligible.