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Serine

Patients receive fludarabine phosphate 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 SC QD on days -8 to -4. Patients then undergo allogeneic PBSC transplant on day 0.

Allogeneic CD56-positive CD3-negative Natural Killer Cells

Allogeneic Hematopoietic Stem Cell Transplantation

Fludarabine Phosphate

Laboratory Biomarker Analysis

Peripheral Blood Stem Cell Transplantation

Pharmacological Study

Richard E Champlin

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.

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.

Donor Natural Killer Cells and Donor Stem Cell Transplant in Treating Patients With High Risk Myeloid Malignancies

NK Cells With HLA Compatible Hematopoietic Transplantation for High Risk Myeloid Malignancies

Participants that experienced DLT related to the NK Cells post transplant at different dose levels.

Participants that survived between day of transplant and day of death on different dose levels.

Number of participants that had grade 3 toxicities up to day 42.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Donor participants only signed the consents and were not part of the results and Adverse events were not collected.

Allogeneic stem cell transplant for patients with high risk myeloid malignancies conditioned with Fludarabine and Busulfan in combination with ex vivo expanded NK cells from 3 different NK cell sources : KIR mismatched haplo donors, KIR mismatched cord blood donors or HLA matched related donors.

Phase I: NK Cell Dose Level 1_10^6

Phase I: NK Cell Dose Level 2_10^7

Phase I: NK Cell Dose Level 3_ 3x10^7

Allogeneic stem cell transplant for patients with high risk myeloid malignancies conditioned with Fludarabine and Busulfan in combination with phase I/II escalation ex vivo expanded NK cells from 3 different NK cell sources : KIR mismatched haplo donors, KIR mismatched cord blood donors or HLA matched related donors.

Phase I: NK Cell Dose Level 4_ 10^8

Phase II: NK Cell Dose Level 3_3x10^7

Allogeneic stem cell transplant for patients with high risk myeloid malignancies conditioned with Fludarabine and Busulfan in combination with phase I/II escalation ex vivo expanded NK cells from 3 different NK cell sources : KIR mismatched haplo donors, KIR mismatched cord blood

Phase II: NK Cell Dose Level 4_ 10^8

Donors: KIR mismatched haplo donors, KIR mismatched cord blood donors or HLA matched related donors.

Spots Global Cancer Trial Database for blasts under 20 percent of bone marrow nucleated cells