Planned Donor Lymphocyte Infusion (DLI) After Allogeneic Stem Cell Transplantation (SCT)
Condition: Leukemia; Lymphoma; Myeloma; Myeloproliferative Diseases
MeSH terms: Myeloproliferative Disorders
Intervention: Fludarabine; Melphalan; Alemtuzumab; Stem Cell Infusion; Tacrolimus; Methotrexate; G-CSF; Low Dose Donor T-Cells; High Dose Donor T-Cells
Intervention description: 40 mg/m^2 by vein on Day -6 to -3.; 140 mg/m^2 by vein on Day -2.; 50 mg by vein on Day -1.; Reduced intensity stem cell transplant on Day 0.; 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35.; 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6.; 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.; Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64.; Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64.
Intervention MeSH terms: Methotrexate; Fludarabine phosphate; Fludarabine; Melphalan; Alemtuzumab; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Blood and Marrow Transplantation; Lymphoma; Myeloma; Myeloproliferative Diseases; Leukemia; Myelodysplastic syndrome; MDS; Hodgkin disease; Multiple myeloma; Fludarabine; Fludarabine Phosphate; Fludara; Melphalan; Alkeran; Tacrolimus; Prograf; Methotrexate; G-CSF; Filgrastim; NeupogenTM; Donor Lymphocyte Infusion; DLI; Allogeneic Stem Cell Transplantation; Graft-vs-host disease; GvHD; T-lymphocytes; T-cells; Alemtuzumab; CAMPATH-1H; Campath

Summary:

      The goal of this clinical research study is to learn what dose of a kind of immune cell
      called T-lymphocytes (T-cells) given as a donor infusion about 8-9 weeks after a stem cell
      transplant has the best results. The safety of this treatment will also be studied. This will
      be tested in patients with leukemia, MDS, lymphoma, Hodgkin disease, and multiple myeloma.
      These results are measured as helping to control the disease without severe graft-versus-host
      disease (GvHD). GvHD is when transplanted donor tissue attacks the tissues of the recipient's
      body.

      Fludarabine, melphalan, and alemtuzumab are commonly given before stem cell transplants:

        -  Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells,
           which may cause the cancer cells to die.

        -  Melphalan is designed to bind to the DNA of cells, which may cause cancer cells to die.

        -  Alemtuzumab is designed to weaken the immune system and reduce the risk of rejection of
           the transplant and graft-vs-host disease (GvHD).

      The donor infusion of T-cells is designed to help restore the immune system after the
      transplant, cause an immune reaction against the cancer, and reduce the risk of the cancer
      coming back.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age >/= 18 years and </= 65 years with one of the following: a. Acute leukemia past
             first remission, in first or subsequent relapse, in second or greater remission.
             Patients in first remission should have intermediate or high cytogenetic risk factors
             or flt3 mutation. Patients with primary induction failure or relapse are eligible if
             they have <10% bone marrow blasts, and no circulating blasts. b. Myelodysplastic
             syndrome with intermediate or high risk IPSS score, or treatment related MDS. c. CML
             resistant to tyrosine kinase inhibitor treatment in a first or subsequent chronic
             phase, or in accelerated phase. d. CLL, Lymphoma or Hodgkin's disease which has failed
             to achieve remission or recurred following initial chemotherapy. Patients must have at
             least a PR to salvage therapy, or low bulk untreated relapse (<2 cm largest mass). e.
             Multiple myeloma which has relapsed or progressed and has achieved a partial response
             to salvage chemotherapy.

          2. Patients must have one of the following donor types identified and willing to donate:
             a. Related donor, HLA-matched for HLA-A, -B, C and DR matched or, b. Matched Unrelated
             Donor (MUD), HLA-matched for HLA A, B, C and DRB1 using allele level typing.

          3. Performance score of at least 80% by Karnofsky or performance score 0 to 2 (ECOG).

          4. Estimated creatinine clearance >40 ml/min (based on serum creatinine)

          5. Bilirubin <1.5 mg/dl except for Gilbert's disease.

          6. ALT < 300 IU/ml d.

          7. Left ventricular ejection fraction equal or greater than 40%.

          8. Pulmonary function test (PFT) demonstrating a diffusion capacity (corrected for
             hemoglobin) of least 50% predicted.

          9. Patient or patient's legal representative able to sign informed consent.

        Exclusion Criteria:

          1. Patients who have had prior autologous transplants or prior allogeneic transplants are
             not eligible.

          2. Uncontrolled active infection.

          3. Positive Beta HCG test in a woman with child bearing potential, defined as not
             post-menopausal for 12 months or no previous surgical sterilization.

          4. Women of child bearing potential not willing to use an effective contraceptive measure
             while on study.

          5. Subject has known sensitivity to any of the products that will be administered during
             the study.

          6. Patients who are HIV seropositive.