Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Condition: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Splenic Marginal Zone Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Waldenstrom Macroglobulinemia
MeSH terms: Burkitt Lymphoma; Mycoses; Lymphoma; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Preleukemia; Neoplasm Metastasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, B-Cell, Marginal Zone; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Mycosis Fungoides; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Sezary Syndrome; Lymphoma, T-Cell, Cutaneous; Waldenstrom Macroglobulinemia; Leukemia, Myelomonocytic, Juvenile; Lymphoma, Large-Cell, Anaplastic; Leukemia, Myeloid, Chronic-Phase; Blast Crisis; Lymphomatoid Granulomatosis; Lymphoma, Extranodal NK-T-Cell; Leukemia, Prolymphocytic; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Large Granular Lymphocytic; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Recurrence
Intervention: double-unit umbilical cord blood transplantation; cytogenetic analysis; bone marrow aspiration; fluorescence in situ hybridization; busulfan; cyclophosphamide; anti-thymocyte globulin; methylprednisolone; cyclosporine; mycophenolate mofetil; flow cytometry; allogeneic hematopoietic stem cell transplantation
Intervention description: Undergo transplantation; Correlative studies; Correlative studies; Correlative studies; Given orally; Given IV; Given IV; Given IV; Given IV; Given orally or IV; Correlative studies; Undergo transplantation
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Busulfan; Cyclosporins; Thymoglobulin; Antilymphocyte Serum; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 12 Years
Maximum age: 64 Years
Healthy volunteers: No

Summary:

      RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant (UCBT) helps
      stop the growth of cancer and abnormal cells and helps stop the patient's immune system from
      rejecting the donor's stem cells. When the stem cells from an unrelated donor, that do not
      exactly match the patient's blood, are infused into the patient they may help the patient's
      bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the
      transplanted cells from a donor can make an immune response against the body's normal cells.
      Giving antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil
      after transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well donor umbilical cord blood stem cell
      transplant works in treating patients with hematologic malignancies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients will be diagnosed with one of the following hematological malignancies: acute
             myelogenous leukemia (AML), acute lymphoblastic leukemia, non-Hodgkin's lymphoma,
             myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and
             myeloproliferative and lymphoproliferative disorders

          -  AML--First remission (CR1) with high risk features including a known prior diagnosis
             of myelodysplasia (MDS); therapy related AML; white cell count at presentation >
             100,000; presence of extramedullary leukemia at diagnosis; unfavorable AML subtype
             (M0, M5-M7); poor cytogenetic markers (abnormalities of chromosome 5, 7 or 8, 11q23,
             Philadelphia chromosome, complex karyotype)

          -  AML--Second remission (CR2) or subsequent remission

          -  AML--Relapse/Persistent Disease with < 20% bone marrow blasts

          -  ALL--First remission (CR1) at high risk for relapse as defined by: B cell ALL white
             blood cell count (WBC) at presentation > 30,000 (T cell ALL WBC > 100,000); presence
             of high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL
             rearrangements (11q23), t(8;14)

          -  ALL--Second remission (CR2) or subsequent remission

          -  ALL--Relapse/Persistent Disease with < 20% bone marrow blasts

          -  Non-Hodgkin Lymphoma--Induction failure or relapse and sensitive to most recent
             chemotherapy

          -  MDS--Low or Intermediate-1 International Prognostic Scoring System (IPSS) score with:
             life-threatening cytopenia(s); and/or red cell or platelet transfusion dependence

          -  MDS--ANC < 500, recurrent infections, PRBC transfusions > 2 units/month, poor risk
             cytogenetics, platelet transfusion dependence

          -  MDS--Intermediate-2 or High IPSS score

          -  CML--Chronic phase I (CP1) and resistant to or intolerant of tyrosine kinase
             inhibitors (i.e. imatinib, dasatinib, etc.)

          -  CML--CP2 or subsequent chronic phase, including chronic phase achieved after induction
             therapy for blast crisis

          -  Myeloproliferative and lymphoproliferative disorders--eligibility to be determined by
             a consensus of the physicians on the Case Comprehensive Cancer Center
             Leukemia/Lymphoma Multidisciplinary Committee

          -  Myeloproliferative and lymphoproliferative disorders--must have evidence of disease
             acceleration to be a candidate for umbilical cord blood transplant; myeloproliferative
             disorders eligible for transplant include chronic myelomonocytic leukemia (CMML) with
             high IPSS score and myelofibrosis

          -  Myeloproliferative and lymphoproliferative disorders--potential lymphoproliferative
             disorders eligible for transplant include chronic lymphocytic leukemia, prolymphocytic
             leukemia, and large granular lymphocytic leukemia

          -  Good performance status: Karnofsky >= 70 % or ECOG 0-1

          -  Calculated creatinine clearance >= 60 mL/min, or measured creatinine clearance >= 60
             mL/min (by 24-hour urine collection) if creatinine >= 1.5 or history of renal
             dysfunction

          -  Hepatic Transaminases < 4 x upper limit normal (ULN); total bilirubin < 2.5 mg/dL,
             unless the patient has a history of benign congenital hyperbilirubinemia (Gilbert's
             syndrome)

          -  Normal cardiac function by echocardiogram or radionuclide scan, (left ventricular
             ejection fraction > 45%); if the left ventricular ejection fraction is between 40-50%,
             clearance by an adult cardiologist is required

          -  Pulmonary function tests demonstrating FEV1 > 60% of predicted for age

          -  Adults must have a DLCOva > 60% normal

          -  For patients unable to complete pulmonary function tests clearance by an adult
             pulmonologist is required

          -  Patients will be eligible for the clinical trial under the following conditions: they
             do NOT have an HLA-A/B/DR B1 identical RELATED bone marrow donor; they do NOT have a
             6/6 HLA-identical matched unrelated adult donor; OR a matched related donor transplant
             is not in the best interest of the patient (i.e., patient's condition precludes
             waiting on the donor, too much time to prepare the donor, the donor is ineligible due
             to medical reasons, or in the case of high risk disease a related donor is not
             appropriated (syngeneic transplant); the decision must be agreed upon by the consensus
             of physicians on the Case Comprehensive Cancer Center Leukemia/Lymphoma
             Multidisciplinary Committee; OR their condition precludes waiting to search and find a
             donor in the National Marrow Donor Registry

        Exclusion Criteria:

          -  Female patients who are pregnant or breast-feeding

          -  HIV or HTLV-1 positivity

          -  Any leukemia with a morphologic relapse or persistent disease in the BM with >= 20%
             blasts (cytogenetic relapse without morphologic evidence of relapse, or cytogenetic
             persistent disease is acceptable)

          -  Active extramedullary leukemia, including CNS disease

          -  Prior hematopoietic stem cell transplant (autologous or allogeneic)

          -  Uncontrolled infection

          -  Patient has an identical related bone marrow donor or a 6/6 HLA-identical matched
             unrelated donor

          -  Any patient who is unable to provide informed consent or comply with the requirements
             of the protocol