Clinical trial NCT00963872 (phase 1/phase 2, status: terminated)
Conditions: leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, C90.01, C90.02, C90.00, D46.9, D46.C, D46.Z
Drugs: cyclophosphamide, fludarabine phosphate
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, NC1=NC(F)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O
Reason stopped: 
    lack of efficacy after interim analysis
  
Eligibility criteria:

        Inclusion Criteria:

          -  Disease Criteria

               -  Acute Leukemias: Must be in remission by morphology (<5% blasts). Note
                  cytogenetic relapse or persistent disease without morphologic relapse is
                  acceptable. Also a small percentage of blasts that is equivocal between marrow
                  regeneration vs. early relapse are acceptable provided there are no associated
                  cytogenetic markers consistent with relapse. (See exclusion criteria for more
                  detailed definition)

               -  Acute myeloid leukemia: high risk CR1 (as evidenced by preceding myelodysplastic
                  syndrome (MDS), high risk cytogenetics such as those associated with MDS or
                  complex karyotype, > 2 cycles to obtain complete remission (CR) or erythroblastic
                  and megakaryocytic); second or greater CR.

               -  Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk
                  cytogenetics (e.g. t(9;22, t(1;19), t(4;11), other MLL rearrangements) or > 1
                  cycle to obtain CR; second or greater CR.

               -  Burkitt's lymphoma in CR2 or subsequent CR

               -  Natural Killer cell malignancies

               -  Myeloproliferative syndromes/diseases: Chronic myelogenous leukemia (CML) in
                  chronic or accelerated phase but patients must have failed or been intolerant to
                  Imatinib mesylate. EXCLUDED: CML in refractory blast crisis, myelofibrosis,
                  polycythemia vera, and essential thrombocytosis.

               -  Myelodysplastic Syndrome: any subtype including refractory anemia (RA) if severe
                  pancytopenia, high risk complex cytogenetics or International Prognostic Scoring
                  System (IPSS) ≥ intermediate-2 (Int-2). Blasts must be less than 5%. If 5% or
                  more requires therapy pre-transplant to reduce blast count to ≤5%. Patients who
                  receive single agent 5-azacytidine, decitabine or immunomodulating drugs are
                  eligible.

               -  Large-cell lymphoma, Hodgkin's lymphoma and multiple myeloma: patients with
                  chemotherapy sensitive disease that has failed or who are ineligible for an
                  autologous transplant. Patients are eligible for umbilical cord blood (UCB)
                  transplantation if there is no evidence of progressive disease by imaging
                  modalities and/or biopsy. Persistent PET activity, though possibly related to
                  lymphoma, IS NOT an exclusion criterion in the absence of computated tomography
                  (CT) changes in size indicating progression. Large-cell and Hodgkin's lymphoma
                  that is progressive on salvage therapy is NOT eligible. Patients with stable
                  disease are eligible for transplantation if the largest residual nodal mass is <
                  5 cm (approximately). For patients who have responded to preceding therapy, the
                  largest residual mass must represent a 50% reduction and be < 7.5 cm
                  (approximately).

               -  Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone
                  B-cell lymphoma, follicular lymphoma which have progressed after at least two
                  prior therapies. Patients with bulky disease should be considered for debulking
                  chemotherapy before transplant. Patients with refractory disease are eligible,
                  unless has bulky disease and an estimated tumor doubling time of less than one
                  month. Patients with stable disease are eligible for transplantation if the
                  largest residual nodal mass is < 5 cm (approximately). For patients who have
                  responded to preceding therapy, the largest residual mass must represent a 50%
                  reduction and be < 7.5 cm (approximately).

               -  Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are
                  eligible after initial therapy if chemotherapy sensitive. Mantle-cell lymphoma
                  that is progressive on salvage therapy is NOT eligible. Patients with stable
                  disease are eligible for transplantation if the largest residual nodal mass is <
                  5 cm (approximately). For patients who have responded to preceding therapy, the
                  largest residual mass must represent a 50% reduction and be < 7.5 cm
                  (approximately).

          -  Umbilical Cord Blood Graft Selection - Two UCB units will be compose the graft, and
             each unit must be a 4-6 HLA-A, B, DRB1 antigen match to each other, as well as a 4-6
             antigen match to the recipient. The combined cryopreserved nucleated cell dose of the
             2 units must be ≥ 3 X 10^7/kg with each unit having a minimum cell dose of 1.5 X
             10^7/kg. UCB units will be selected according to a common umbilical cord blood graft
             selection algorithm

          -  Performance Status - adequate performance status defined as Karnofsky score ≥ 60

          -  Age 18 to 70 years of age; patients ≥ 70 but ≤ 75 years are eligible if the
             co-morbidity score is ≤ 2

          -  Organ Function

               -  Cardiac: Left ventricular ejection fraction > 35%; absence of decompensated
                  congestive heart failure; absence of uncontrolled arrhythmia

               -  Pulmonary: DLCO > 30% of predicted; absence of O2 requirements

               -  Hepatic: ALT, AST, alkaline phosphatase and bilirubin < 5 x upper limit of normal

               -  Renal: Creatinine ≤ 2 mg/dl (patients with a creatinine > 1.2 or history of renal
                  dysfunction must have calculated glomerular filtration rate (GFR) > 40
                  mL/min/1.73m2)

               -  If recent mold infection e.g. Aspergillus - must have minimum of 30 days of
                  appropriate treatment before transplant and infection controlled and be cleared
                  by Infectious Disease.

               -  The following conditions must be met:

                    -  If prior myeloablative autologous transplant, must be > 3 months but ≤ 12
                       months from transplant OR have received at least 2 cycles of multi-agent or
                       highly immunosuppressive chemotherapy (i.e. induction for acute leukemia)
                       within the 3 months preceding this study. OR

                    -  If neither prior myeloablative autologous transplant ≤ 12 months from
                       transplant nor have received at least 2 cycles of multi-agent or highly
                       immunosuppressive chemotherapy (i.e. induction for acute leukemia) within
                       the 3 months preceding this study, patients are eligible as long as they
                       receive equine anti-thymocyte globulin as part of the conditioning regimen.

        Exclusion Criteria:

          -  Patients who have an available, medically suitable, 5-6/6 HLA-A, B, DRB1 matched
             sibling donor

          -  Patients who are eligible for autologous transplantation

          -  Prior allogeneic transplant

          -  Acquired or inherited bone marrow failure syndromes such as aplastic anemia and
             Fanconi anemia

          -  Pregnant or breast feeding

          -  Evidence of HIV infection or known HIV positive serology

          -  Current uncontrolled serious infection

          -  Active central nervous system malignancy