Donor Natural Killer Cells and Aldesleukin in Treating Patients w/High Risk AML Undergoing Donor Stem Cell Transplant
Condition: Acute Myelogenous Leukemia
MeSH terms: Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Giving chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total
      body irradiation, before peripheral blood stem cell transplant helps stop the growth of
      cancer cells. It may also stop the patient's immune system from rejecting the donor's stem
      cells. When the healthy stem cells and natural killer (NK) 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. Giving IL-2 (aldesleukin) after NK cell infusion may
      stimulate them to kill any remaining cancer cells.

      PURPOSE: This phase I/II (currently enrolling in phase II) trial is studying how well a donor
      natural killer cell infusion works in treating patients who are undergoing donor stem cell
      transplant for acute myeloid leukemia.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To determine the disease-free survival at 6 months and 1 year in patients with high-risk
           myeloid malignancies who undergo a reduced-intensity haploidentical hematopoietic stem
           cell transplantation (HSCT) supplemented with donor natural killer (NK) cells.

      Secondary

        -  To evaluate the in vivo expansion of a donor CD3- CD19- selected NK cell product
           administered after a preparative regimen of cyclophosphamide, fludarabine, and total
           body irradiation (TBI) and HSCT in these patients.

        -  To determine the rate of graft failure defined by absolute neutrophil count (ANC) <
           500/mm³ by day 28.

        -  To determine the incidence of grade III-IV acute graft-versus-host disease (GVHD) at 6
           months.

        -  To determine the rate of treatment-related mortality at day 100.

        -  To determine the incidence of chronic GVHD at 12 months.

        -  To determine the incidence of disease relapse at 12 months.

        -  To determine the incidence of post-transplant lymphoproliferative disorder at 12 months.

      Correlative

        -  To correlate immune reconstitution of the in vivo expanded haploidentical NK cells with
           clinical outcomes.

      OUTLINE: This is an open-label study.

      Patients receive fludarabine intravenous (IV) over 1 hour on days -18 to -14 and
      cyclophosphamide IV over 2 hours on days -16 and -15. Patients receive cyclosporin A on Day
      -15 through Day -8. Patients undergo total body irradiation on day -13. Patients then receive
      an infusion of donor natural killer cells on day -12 and interleukin-2 subcutaneously on
      alternating days between days -12 to -2. Patients receive thymoglobulin (ATG) and undergo
      allogeneic peripheral blood stem cell transplantation on day 0.

      After completion of study treatment, patients are followed periodically.

      PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.
    

Intervention name(s): aldesleukin; natural killer cells; cyclophosphamide; fludarabine phosphate; allogeneic hematopoietic stem cell transplantation; total body irradiation; Thymoglobulin; Cyclosporin A; cyclophosphamide; fludarabine phosphate
Intervention type(s): Biological; Biological; Drug; Drug; Procedure; Radiation; Biological; Drug; Drug; Drug
Intervention description(s): Administered subcutaneously (SQ) 9 million units every other day beginning Day -12 through -2 (evening of natural killer cell infusion) for a total of 6 doses.; Infusion given on Day -12; The targeted infused cell dose of CD3- CD19- selected NK product is within the range of 2-3 x 10^7 cells/kg.; Administered intravenously (IV) 50 mg/kg on Day -15; Administered intravenously (IV) 40 mg/m^2 on Days -18 through -14; On day 0, patients will receive an allogeneic transplant using pool cells from the day -1 and day 0 PBSC which will be CD34+ selected as the donor graft. The graft will be infused over 15-60 minutes.; Administered on Day -13, 200 cGy two times.; intravenous (IV) 3 mg/kg on Day 0 (day of donor CD34 cell infusion); 1.5 mg/kg by mouth or intravenously for target dose range of 150-250; day -15 through day -8.; Administered intravenously (IV) 50 mg/kg on Days -16 and -15; Administered intravenously (IV) 35 mg/m^2 on Days -18 through -14
Other intervention name(s): Interleukin-2; IL-2; therapeutic allogeneic lymphocytes; Cytoxan; Fludara; PBSC; rabbit ATG; CSA; Cytoxan; Fludara
Intervention MeSH terms: Vidarabine; Aldesleukin; Cyclosporine; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2; Cyclosporins; Thymoglobulin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: NK cells; natural killer cells; immunotherapy; hematopoietic cell transplant; acute myelogenous leukemia