Clinical trial NCT00376519 (phase 1, status: terminated)
Conditions: graft versus host disease, leukemia, lymphoma, multiple myeloma and plasma cell neoplasm, myelodysplastic syndromes, secondary myelofibrosis
ICD codes: D89.810, D89.811, D89.813, D89.812, 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, C96.20, C96.29, D47.09, D46.9, D46.C, D46.Z, D75.81, C94.41, C94.42, C94.40
Drugs: cyclophosphamide, cyclosporine, fludarabine phosphate, mycophenolate mofetil
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C, NC1=NC(F)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O, N[C@@H](CCCNC(N)=N)C(O)=O
Reason stopped: 
    slow accrual
  
Eligibility criteria:

        Inclusion Criteria:

        Patient and Donor Demographic Criteria

          -  Patient must be 18-45 years of age.

          -  Patients must have three partially HLA matched UCB units. Units identified as the HSC
             source must be HLA matched at 4-6 HLA- A and B (at low to intermediate resolution) and
             DRB1 (at high resolution), and the units must be HLA matched at 4-6 HLA- A, B, DRB1
             antigens with each other. Total cryopreserved HSC graft cell dose must be >2.5 x 107
             nucleated cells per kilogram recipient body weight. Also, the two umbilical cord blood
             (UCB) units must be ABO-matched.

          -  The UCB unit identified as the Treg source must be HLA matched at 4-6 HLA antigens
             with the patient (without an HLA or ABO matching criterion with the UCB HSC source).

        Disease Criteria

          -  Patients must have a hematological malignancy as listed below:

               -  Acute myelogenous leukemia: high risk CR1 (as evidenced by preceding
                  myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated
                  with MDS or complex karyotype, or >2 cycles to obtain complete remission (CR);
                  second or greater CR. Must be in remission by morphology (<5% blasts within
                  normocellular marrow).

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

          -  Chronic myelogenous leukemia resistant to imatinib therapy

          -  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 (otherwise induction chemotherapy to
             achieve < 10% blasts is required pre-transplant).

          -  Advanced myelofibrosis

          -  Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone
             B-cell lymphoma or follicular lymphoma that have progressed 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 non-Hodgkins lymphoma (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 will have a Karnofsky score > 80% and have acceptable organ function ie
             creatinine < 2.0, bilirubin, AST/ALT, ALP < 2 x normal, pulmonary function > 50%
             normal, left ventricular ejection fraction > 45%. Note: All patients with a creatinine
             > 1.2 or a history of renal dysfunction must have creatinine clearance (must be > 40
             ml/min to be eligible).

          -  Recipients will sign informed consent approved by the Committee on the Use of Human
             Subjects at the University of Minnesota.

        Exclusion Criteria:

          -  Pregnant or breastfeeding

          -  Evidence of HIV infection or known HIV positive serology

          -  Current active infection

          -  Available HLA matched sibling donor.

          -  CML in active blast crisis