Donor Natural Killer Cells and Donor Stem Cell Transplant in Treating Patients With High Risk Myeloid Malignancies
Condition: Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Erythroid Leukemia; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blasts Under 20 Percent of Bone Marrow Nucleated Cells; Blasts Under 20 Percent of Peripheral Blood White Cells; Chronic Myelomonocytic Leukemia; High Risk Myelodysplastic Syndrome; Myelodysplastic Syndrome; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Myeloid, Accelerated Phase; Leukemia, Megakaryoblastic, Acute; Blast Crisis; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This phase I/II trial studies the side effects and best dose of donor natural killer cells
      when given together with donor stem cell transplant and to see how well they work in treating
      patients with myeloid malignancies that are likely to come back or spread. Giving
      chemotherapy, such as busulfan and fludarabine phosphate, before a donor 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 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 OBJECTIVES:

      I. Assess the safety of infusing ex vivo expanded natural killer (NK) cells in patients
      receiving busulfan-fludarabine phosphate (fludarabine) with an allogeneic human leukocyte
      antigen (HLA) matched hematopoietic transplantation for myeloid malignancies. Two sources of
      NK cells could be studied, depending on what donor source is available: cells from the HLA
      matched related donor or cells from an unrelated cord blood unit.

      II. For each source of NK cells: the maximum tolerated cell dose; the phenotype and function
      of the ex vivo expanded NK cells and their survival in vivo; the rate of engraftment,
      graft-vs.-host disease (GVHD), immune reconstitution, relapse rates and survival for patients
      receiving this regimen will be determined.

      OUTLINE: This is a phase I, dose-escalation study of NK cells followed by a phase II study.

      Patients receive fludarabine phosphate intravenously (IV) over 1 hour and busulfan IV over 3
      hours on days -13 to -10. Patients then receive allogeneic CD56-positive CD3-negative natural
      killer cells IV over 1 hour on day -8. Patients also receive aldesleukin subcutaneously (SC)
      once daily (QD) on days -8 to -4. Patients then undergo allogeneic peripheral blood stem cell
      (PBSC) transplant on day 0.
    

Intervention name(s): Aldesleukin; Allogeneic CD56-positive CD3-negative Natural Killer Cells; Allogeneic Hematopoietic Stem Cell Transplantation; Busulfan; Fludarabine Phosphate; Laboratory Biomarker Analysis; Peripheral Blood Stem Cell Transplantation; Pharmacological Study
Intervention type(s): Biological; Biological; Procedure; Drug; Drug; Other; Procedure; Other
Intervention description(s): Given SC; Given IV; Undergo allogeneic PBSC transplant; Given IV; Given IV; Correlative studies; Undergo allogeneic PBSC transplant; Correlative studies
Other intervention name(s): 125-L-Serine-2-133-interleukin 2; Proleukin; r-serHuIL-2; Recombinant Human IL-2; Recombinant Human Interleukin-2; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; 1, 4-Bis[methanesulfonoxy]butane; BUS; Bussulfam; Busulfanum; Busulfex; Busulphan; CB 2041; CB-2041; Glyzophrol; GT 41; GT-41; Joacamine; Methanesulfonic Acid Tetramethylene Ester; Methanesulfonic acid, tetramethylene ester; Mielucin; Misulban; Misulfan; Mitosan; Myeleukon; Myeloleukon; Myelosan; Mylecytan; Myleran; Sulfabutin; Tetramethylene Bis(methanesulfonate); Tetramethylene bis[methanesulfonate]; WR-19508; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586; PBPC transplantation; PBSCT; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplant; Peripheral Stem Cell Transplantation
Intervention MeSH terms: Aldesleukin; Fludarabine; Fludarabine phosphate; Busulfan; Interleukin-2
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment