Natural Killer Cells Before and After Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia
Condition: Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia With Gene Mutations; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Therapy-Related Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Myelodysplastic Syndromes; Syndrome; Recurrence
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This phase I/II studies the side effects and best dose of natural killer cells before and
      after donor stem cell transplant and to see how well they work in treating patients with
      acute myeloid leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia. Giving
      chemotherapy with or without total body irradiation before a donor peripheral blood stem cell
      or bone marrow 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 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.
    

Detailed description: 
      PRIMARY OBJECTIVE:

      I. To evaluate safety, tolerability and identify the maximum tolerated dose (MTD) of expanded
      natural killer (NK) cells to be used in patients with myeloid malignancies undergoing a
      haploidentical stem-cell transplant.

      SECONDARY OBJECTIVES:

      I. To determine survival of NK cells in vivo post-transplant. II. To determine the function
      of NK cells post-transplant and compare with a retrospective control treated with no NK
      cells.

      III. To estimate the proportion of patients with engraftment/graft failure. IV. To estimate
      the non-relapse mortality (NRM) at day 100 post-transplant. V. To estimate the cumulative
      incidence of grade III-IV aGVHD (acute graft-versus-host disease) at day 100.

      VI. To assess the rate of chronic graft-versus-host disease (GVHD) within the first year post
      transplantation.

      VII. To assess immune reconstitution post-transplant. VIII. To assess disease response,
      disease-free survival (DFS) and overall survival (OS) after transplantation.

      IX. To perform a retrospective comparison of patients treated on the study with NK cells will
      be performed with a Center for International Blood and Marrow Transplant Research (CIBMTR)
      control of similar patients who did not receive NK cells.

      OUTLINE: This is a phase I, dose-escalation study of NK cells followed by a phase II study.
      Patients are assigned to 1 of 2 conditioning regimens.

      MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan intravenously (IV)
      over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo total-body
      irradiation (TBI) on day -3, and NK cells IV over 30 minutes on day -2 or -1.

      NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day
      -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells
      IV over 30 minutes on day -2 or -1.

      TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell (PBSC) or bone marrow
      transplant on day 0.

      POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV
      over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then orally
      (PO) for approximately 4 months, and mycophenolate mofetil PO thrice daily (TID) beginning on
      day 5 for approximately 6-7 months.

      NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90.

      After completion of study treatment, patients are followed up for 2 years.
    

Intervention name(s): Allogeneic Hematopoietic Stem Cell Transplantation; Bone Marrow Transplantation; Cyclophosphamide; Fludarabine; Laboratory Biomarker Analysis; Melphalan; Mycophenolate Mofetil; Natural Killer Cell Therapy; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Total-Body Irradiation
Intervention type(s): Procedure; Procedure; Drug; Drug; Other; Drug; Drug; Biological; Procedure; Drug; Radiation
Intervention description(s): Undergo allogeneic PBSC or bone marrow transplant; Undergo allogeneic PBSC or bone marrow transplant; Given IV; Given IV; Correlative studies; Given IV; Given PO; Given IV; Undergo allogeneic PBSC or bone marrow transplant; Given IV and PO; Undergo TBI
Other intervention name(s): Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Blood and Bone Marrow Transplant; BMT; Bone Marrow Grafting; Bone Marrow Transplant; Marrow Transplantation; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Fluradosa; Alanine Nitrogen Mustard; CB-3025; L-PAM; L-Phenylalanine Mustard; L-Sarcolysin; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Phenylalanine Nitrogen Mustard; Sarcoclorin; Sarkolysin; WR-19813; CellCept; MMF; PBPC transplantation; PBSCT; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplant; Peripheral Stem Cell Transplantation; FK 506; Fujimycin; Hecoria; Prograf; Protopic; SCT_TBI; TBI; Total Body Irradiation; Whole Body Irradiation; Whole-Body Irradiation
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Melphalan; Mechlorethamine; Nitrogen Mustard Compounds; Fludarabine; Tacrolimus
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment