Donor Natural Killer Cell Therapy and Aldesleukin in Treating Patients With High Risk Acute Myeloid Leukemia Undergoing Donor Stem Cell Transplant
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.
Acute Myelogenous Leukemia
Biological: natural killer cells
Drug: fludarabine phosphate
Procedure: allogeneic hematopoietic stem cell transplantation
Radiation: total body irradiation
Drug: Cyclosporin A
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Reduced Intensity Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) Supplemented With Donor Natural Killer (NK) Cell Infusions in Patients With High Risk Myeloid Malignancies Who Are Unsuitable for Fully Myeloablative Transplantation|
- Disease-free survival [ Time Frame: Month 6, 1 Year ] [ Designated as safety issue: No ]
- In vivo expansion of a donor CD3- CD19- selected NK cell product [ Time Frame: Day -1 (12 days after NK cell infusion) ] [ Designated as safety issue: No ]
- Rate of graft failure [ Time Frame: Day 28 ] [ Designated as safety issue: No ]Measured by <500 absolute neutrophile count by day 28.
- Incidence of grade III-IV acute Graft Versus Host Disease [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
- Rate of treatment-related mortality [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
- Incidence of chronic Graft Versus Host Disease [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
- Incidence of disease relapse [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
- Incidence of post-transplant lymphoproliferative disorder [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
|Study Start Date:||January 2005|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: Stem Cell Transplant with Donor Natural Killer Cells
Patients with high risk myeloid malignancies undergoing hematopoeitic stem cell transplant receiving donor natural killer cells.
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.
Other Names:Biological: natural killer cells
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.
Other Name: therapeutic allogeneic lymphocytesDrug: cyclophosphamide
Administered intravenously (IV) 50 mg/kg on Days -16 and -15
Other Name: CytoxanDrug: fludarabine phosphate
Administered intravenously (IV) 35 mg/m^2 on Days -18 through -14
Other Name: FludaraProcedure: allogeneic hematopoietic stem cell transplantation
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.
Other Name: PBSCRadiation: total body irradiation
Administered on Day -13, 200 cGy two times.Biological: Thymoglobulin
intravenous (IV) 3 mg/kg on Day 0 (day of donor CD34 cell infusion)
Other Name: rabbit ATGDrug: Cyclosporin A
1.5 mg/kg by mouth or intravenously for target dose range of 150-250; day -15 through day -8.
Other Name: CSA
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00303667
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Sarah Cooley, MD||Masonic Cancer Center, University of Minnesota|