Myeloablative Umbilical Cord Blood Transplantation in Hematological Diseases
Condition: Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; MDS; Refractory Anemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Non-Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma; Myelodysplastic Syndromes
MeSH terms: Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Prolymphocytic; Anemia; Myelodysplastic Syndromes; Primary Myelofibrosis; Anemia, Refractory; Hematologic Diseases; Syndrome
Intervention: filgrastim; cyclophosphamide; cyclosporine; fludarabine phosphate; mycophenolate mofetil; umbilical cord blood transplantation; total-body irradiation
Intervention description: All patients will receive G-CSF 5 mcg/kg/day intravenously(IV) (dose rounded to vial size) based on the actual body weight IV beginning on day +1 after umbilical cord blood (UCB) infusion. G-CSF will be administered daily until the absolute neutrophil count (ANC) exceeds 2.5 x 10^9/L for three consecutive days.; Cyclophosphamide to be administered with high volume fluid flush and mesna (MT(S) 9006) at 10:00am, or per institutional routine, on days-7 and -6 after fludarabine. Cyclophosphamide 60mg/kg/day intravenous (IV) x 2 days, total dose 120 mg/kg (days -7 and -6) Dosing is calculated based on Actual BodyWeight (ABW) unless ABW > 30 kg above Ideal BodyWeight (IBW), in which case the dose should be computed using adjusted body weight.; Patients will receive cyclosporine (CSA) therapy beginning on day -3 maintaining a level of > 200 ng/mL. For adults the initial dose will be 2.5 mg/kg intravenously (IV) over 2 hours every 12 hours. For children < 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours.; Fludarabine 25 mg/m2/day intravenously (IV) x 3 days, total dose 75 mg/m2 (days -8 to -6);; All patients will begin mycophenolate mofetil (MMF) on day -3. Patients ≥ 40 kilograms will receive MMF at the dose of 3 grams/day divided into 2 or 3 doses (every 12 or 8 hours).
Pediatric patient (<40 kilograms) will receive MMF at the dose of 15 mg/kg three times a day.; The product is infused via intravenous (IV) drip directly into the central line without a needle, pump or filter.; The recommended TBI is 165 cGy given twice daily for a total dose of 1320 cGy (days -4 to -1).
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 213.0
Sex: All
Maximum age: 55 Years
Healthy volunteers: No
Keywords: blastic phase chronic myelogenous leukemia; primary myelofibrosis; chronic myelomonocytic leukemia; myelodysplastic syndromes; juvenile myelomonocytic leukemia; recurrent adult Burkitt lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent lymphoblastic lymphoma; recurrent childhood acute myeloid leukemia; recurrent childhood large cell lymphoma; recurrent follicular lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; refractory chronic lymphocytic leukemia; refractory multiple myeloma; chronic myelogenous leukemia; secondary acute myeloid leukemia; secondary myelodysplastic syndromes; multiple myeloma; adult lymphoblastic lymphoma; refractory anemia with excess blasts; refractory anemia; Burkitt lymphoma; childhood large cell lymphoma; adult Burkitt lymphoma; mantle cell lymphoma; childhood lymphoblastic lymphoma; childhood myelodysplastic syndromes

Summary:

      RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, and
      total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop
      the growth of cancer cells and prepares the patient's bone marrow for the stem 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. Sometimes the
      transplanted cells from a donor can make an immune response against the body's normal cells.
      Giving cyclosporine and mycophenolate mofetil may stop this from happening.

      PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide
      together with total-body irradiation works in treating patients who are undergoing an
      umbilical cord blood transplant for hematologic cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Acute myeloid leukemia (AML): high risk CR1 (as evidenced by preceding myelodysplastic
             syndrome [MDS], high risk cytogenetics, ≥ 2 cycles to obtain complete remission [CR],
             erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined
             by hematological recovery, AND <5% blasts by light microscopy within the bone marrow
             with a cellularity of ≥15%.

          -  Very high risk pediatric patients with AML. Patients <21 years, however, are eligible
             with (M2 marrow) with < or = 25% blasts in marrow after having failed one or more
             cycles of chemotherapy. This group of patients will be analyzed separately.

          -  Acute lymphocytic leukemia (ALL): high risk CR1 [t(9;22), t (1:19), t(4;11) or other
             MLL rearrangements] hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle
             to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are
             eligible. All patients must be in CR as defined by hematological recovery, AND <5%
             blasts by light microscopy within the bone marrow with a cellularity of ≥15%.

          -  Very high risk pediatric patients with ALL. patients <21 years are also considered
             high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction
             or M3 marrow at the end of induction. They are eligible once they achieved a complete
             remission

          -  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.

          -  Plasma Cell leukemia after initial therapy, who achieved at least a partial remission

          -  Advanced myelofibrosis

          -  Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia
             with severe pancytopenia or high risk cytogenetics. Blasts must be < 10% by a
             representative bone marrow aspirate morphology.

          -  Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone
             B-cell lymphoma or follicular lymphoma are eligible if there was disease
             progression/relapse within 12 of achieving a partial or complete remission. Patients
             who had remissions lasting > 12 months, are eligible 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 PR1+.

          -  Large cell NHL > CR2/> PR2. Patients in CR2/PR2 with initial short remission (<6
             months) are eligible.

          -  Lymphoblastic lymphoma, Burkitt's 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 β-2 microglobulin > 3 mg/L, may be considered for this
             protocol after initial therapy.

          -  Recipients must have a Karnofsky score (adults) ≥ 80 % or Lansky score ≥ 50%
             (pediatrics), and proper organ function.

        Exclusion Criteria

          -  Active infection at time of transplantation

          -  History of human immunodeficiency virus (HIV) infection

          -  Pregnant or breast feeding.

          -  Chemotherapy refractory large cell and high grade NHL

          -  If < or = 18 years old, prior myeloablative transplant within the last 6 months. If
             >18 years old prior myeloablative allotransplant or autologous transplant

          -  Extensive prior therapy including > 12 months alkylator therapy or > 6 months
             alkylator therapy with extensive radiation.

          -  Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as
             part of their salvage therapy.