Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematological Cancer or Other Disease
Condition: Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: anti-thymocyte globulin; cyclophosphamide; cyclosporine; fludarabine phosphate; mycophenolate mofetil; umbilical cord blood transplantation; total body irradiation
Intervention description: 30mg/Kg Days -6 to -4; 50 mg/Kg Day -6; Patients will receive cyclosporine A (CSA) therapy beginning on Day -3 maintaining a trough level between 250 and 500 ng/mL. For adults the initial dose will be 2.5 mg/kg IV over 1 hour every 12 hours. For children < 40 kg the initial dose will be 2.5 mg/kg IV over 1 hour every 8 hours.; 40mg/m2 Days -6 to -2; 1 gram every 8 hours for patients who are ≥ 40 kg. Pediatric patients (<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours. Stop MMF at Day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD.; Single or double unit umbilical cord blood transplant; 200 cGy Day -1
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Cyclosporins; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Maximum age: 69 Years
Healthy volunteers: No
Keywords: chronic myelogenous leukemia; acute lymphoblastic leukemia; acute myeloid leukemia; atypical chronic myeloid leukemia; chronic myelomonocytic leukemia; anaplastic large cell lymphoma; splenic marginal zone lymphoma; nodal marginal zone B-cell lymphoma; recurrent adult Hodgkin lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent childhood large cell lymphoma; recurrent mycosis fungoides/Sezary syndrome; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; recurrent/refractory childhood Hodgkin lymphoma; childhood diffuse large cell lymphoma; childhood immunoblastic large cell lymphoma; refractory multiple myeloma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; myelodysplastic/myeloproliferative disease; childhood myelodysplastic syndromes; recurrent childhood anaplastic large cell lymphoma; refractory anemia; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory cytopenia with multilineage dysplasia; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage III childhood anaplastic large cell lymphoma; stage III childhood large cell lymphoma; stage IV childhood anaplastic large cell lymphoma; stage IV childhood large cell lymphoma; stage III adult Hodgkin lymphoma; stage III childhood Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; stage IV childhood Hodgkin lymphoma; stage II multiple myeloma; stage III multiple myeloma; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; Waldenstrom macroglobulinemia; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; stage III mycosis fungoides/Sezary syndrome; stage IV mycosis fungoides/Sezary syndrome; juvenile myelomonocytic leukemia; chronic eosinophilic leukemia; chronic idiopathic myelofibrosis; chronic neutrophilic leukemia; essential thrombocythemia; polycythemia vera

Summary:

      RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor
      umbilical cord blood transplant helps stop the growth of cancer or abnormal cells. It may
      also stop the patient's immune system from rejecting the donor's stem cells. The donated stem
      cells may replace the patient's immune cells and help destroy any remaining cancer cells
      (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an
      immune response against the body's normal cells. Giving cyclosporine and mycophenolate
      mofetil before and after transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well donor umbilical cord blood transplant with
      reduced intensity conditioning works in treating patients with advanced hematological cancer
      or other disease.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of advanced hematologic malignancy or other disease not curable by
             conventional chemotherapy, including any of the following:

               -  Acute myeloid leukemia in complete remission (CR)* (as defined by hematologic
                  recovery, < 5% blasts in the bone marrow by morphology, and a cellularity of >
                  15%), meeting one of the following criteria:

                    -  In first complete remission (CR1) AND has high-risk disease as evidenced by
                       any of the following:

                         -  Preceding myelodysplastic syndromes (MDS)

                         -  High-risk cytogenetics (e.g., monosomy 5 or 7, or as defined by
                            referring institution treatment protocol)

                         -  Required > 2 courses of therapy to obtain CR

                         -  Erythroblastic or megakaryocytic leukemia

                    -  In second CR (CR2) or beyond

               -  Acute lymphoblastic leukemia in CR* (as defined by hematologic recovery, < 5%
                  blasts in the bone marrow by morphology, and a cellularity of > 15%), meeting one
                  of the following criteria:

                    -  In CR1 AND has high-risk disease as evidenced by any of the following:

                         -  t(9;22), t(1;19), t(4;11), or other MLL rearrangements

                         -  Hyplodiploid

                         -  Required > 1 course of therapy to obtain CR

                    -  Beyond CR2

               -  Chronic myelogenous leukemia (CML)

                    -  All types are allowed (except refractory blast crisis CML)

                    -  Patients in chronic phase CML must have failed or been intolerant to prior
                       imatinib mesylate (Gleevec) or other tyrosine kinase inhibitors

               -  MDS

                    -  Any subtype allowed (including refractory anemia [RA])

                    -  Severe pancytopenia or complex cytogenetics

                    -  Blasts must be < 5% (if blasts are ≥ 5%, pre-transplant induction therapy is
                       required to reduce blast count to < 5%)

               -  Large cell lymphoma, Hodgkin lymphoma, or multiple myeloma, meeting one of the
                  following criteria:

                    -  Chemotherapy-sensitive disease that has failed prior therapy

                         -  Patients with large cell lymphoma or Hodgkin lymphoma must not have
                            progressive disease during salvage therapy (stable disease allowed
                            provided it is non-bulky)

                    -  Ineligible for an autologous stem cell transplant

               -  Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone
                  B-cell lymphoma, or follicular lymphoma that has progressed after ≥ 2 prior
                  therapies

                    -  Patients with bulky disease should be considered for debulking chemotherapy
                       prior to transplant

                    -  Patients with refractory disease are eligible provided disease is non-bulky
                       AND an estimated tumor doubling time is ≥ 1 month

               -  Lymphoplasmacytic lymphoma, mantle cell lymphoma, or prolymphocytic leukemia

                    -  Chemotherapy-sensitive disease that was previously treated with initial
                       therapy

                         -  Patients with mantle cell lymphoma must not have progressive disease
                            during salvage therapy (stable disease allowed provided it is
                            non-bulky)

               -  Mycosis fungoides and Sezary syndrome

               -  Bone marrow failure syndromes, except for Fanconi anemia

               -  Myeloproliferative syndromes NOTE: *Patients for whom adequate marrow/biopsy
                  specimens can not be obtained to determine remission status by morphologic
                  assessment must have fulfilled criteria of remission (< 5% blasts by flow
                  cytometry and recovery of peripheral blood counts with no circulating blasts)

          -  Ineligible for autologous stem cell transplant due to any of the following:

               -  Prior autologous stem cell transplant

               -  Inadequate autologous stem cell harvest

               -  Inability to withstand a myeloablative preparative regimen

               -  Clinically aggressive/high-risk disease

          -  No evidence of progressive disease by imaging modalities or biopsy (persistent PET
             scan activity allowed provided there are no CT scan changes indicating progression)

          -  Acute leukemia that is refractory, persistent, or relapsed (defined as > 5% blasts in
             normocellular bone marrow) allowed provided patient was rendered aplastic either by
             induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy

          -  Patients with stable disease are eligible provided the largest residual nodal mass is
             approximately < 5 cm (largest residual mass must represent a 50% reduction and be
             approximately < 7.5 cm for patients who have responded to prior therapy)

          -  No active CNS malignancy

          -  Umbilical cord blood (UCB) donor available

               -  UCB graft matched at 4/6 HLA-A, -B, and -DRB1 antigens with the recipient

                    -  May include 0-2 antigen mismatches at the A, B, or DRB1 loci

                    -  Unit selection based on cryopreserved nucleated cell dose and HLA-A, -B, and
                       -DRB1 using intermediate resolution A, B antigen and DRB1 allele typing

               -  If 2 UCB units are required to reach the target cell dose, each unit must be a
                  3/6 HLA-A, -B, and -DRB1 antigen match to each other, as well as a 4/6 antigen
                  match to the recipient

               -  No 5-6/6 HLA-A, -B, and -DRB1 matched sibling donor available

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status (PS) 60-100% OR Lansky PS 50-100%

          -  Creatinine ≤ 2.0 mg/dL (adults) OR creatinine clearance > 40 mL/min (pediatrics)

               -  Adult patients with a creatinine > 1.2 mg/dL or a history of renal dysfunction
                  must have an estimated creatinine clearance of > 40 mL/min

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  LVEF ≥ 35%

          -  DLCO > 30% predicted

          -  No requirement for O_2

          -  No decompensated congestive heart failure

          -  No uncontrolled arrhythmia

          -  None of the following liver diseases or conditions:

               -  Fulminant liver failure

               -  Cirrhosis with evidence of portal hypertension or bridging fibrosis

               -  Alcoholic hepatitis

               -  Esophageal varices

               -  History of bleeding esophageal varices, hepatic encephalopathy, or correctable
                  hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin
                  time

               -  Ascites related to portal hypertension

               -  Bacterial or fungal abscess

               -  Biliary obstruction

               -  Chronic viral hepatitis with total serum bilirubin > 3 mg/dL

               -  Symptomatic biliary disease

          -  Recent mold infection (e.g., Aspergillus) allowed provided patient received ≥ 30 days
             of appropriate treatment AND infection is controlled and cleared by Infectious Disease

          -  No evidence of HIV infection or known HIV-positive serology

          -  No uncontrolled viral or bacterial infection

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  At least 3 months since prior myeloablative stem cell transplantation