RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord 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. Giving interleukin-2 (IL-2, aldesleukin) after transplant may stimulate the natural killer cells to kill any remaining cancer cells. PURPOSE: This phase II trial is studying the side effects of giving combination chemotherapy together with total-body irradiation followed by interleukin-2 (IL-2, aldesleukin), and umbilical cord blood transplant and to see how well it works in treating patients with relapsed or refractory acute myeloid leukemia.
OBJECTIVES: Primary * To determine the rate of neutrophil engraftment and grade III-IV acute graft-versus-host disease (GVHD) following a T cell depleted (TCD) umbilical cord blood (UCB) transplantation without post-transplant immunosuppression followed by administration of interleukin-2 (IL-2, aldesleukin) (every other day) days +3 to +13 to expand NK cells in vivo. Secondary * To evaluate the safety of this regimen as assessed by monitoring the rates of graft failure, acute GVHD, and transplant-related mortality (TRM). * To perform quantitative, phenotypic, and functional assessments of the in vivo expanded UCB-derived NK cells on (day +72). * To assess clinical disease response (leukemia clearance and complete remission) and survival duration in these patients. * To evaluate the tolerability of aldesleukin in these patients. * To evaluate the tolerance of IL-2 OUTLINE: * Preparative regimen: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -7 to -5 and cyclophosphamide IV on days -7 and -6. Patients undergo total-body irradiation twice daily on days -5 to -2. * Transplantation: Patients undergo T-cell depleted umbilical cord blood (UCB) transplantation on day 0. * IL-2 (Aldesleukin) therapy: Patients receive aldesleukin subcutaneously on days +3 6 doses every other day) and +60 (6 doses every other day). Patients are followed periodically for up to 2 years after transplant.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
IL-2 will be administered (9 million units; 5 million units if weight is less than 45 kg) every other day beginning on day +3 for a total of 6 doses and again on day +60 every other day for 6 doses.
60 mg/kg over 1 hour intravenously (IV) on days -7 and -6.
25 mg/m\^2 intravenously (IV) over 1 hour on days -7 through -5.
On day 0, transplantation will occur with double T-cell depleted (TCD) umbilical cord blood (UCB) units
administered on days -5 through -2; 330 cGy daily
University of Minnesota Children's Hospital - Fairview
Minneapolis, Minnesota, United States
Number of Patients With Neutrophil Engraftment
Number of patient with absolute neutrophils \>500\*10\^8/kg by 42 days post transplant.
Time frame: Day 42
Number of Patients With Grade III-IV Acute Graft-Versus-Host (GVHD) Disease
Number of patients with Grade III-IV GVHD. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Acute GVHD usually happens within the first 3 months after transplant.
Time frame: Day 100 Post Transplant
Incidence of Primary Graft Failure
Incidence of graft failure defined as an absolute neutrophil count of less than 500/uL and a bone marrow that is less than 5% cellular (marrow aplasia) on day 42.
Time frame: Day 42
Number of Patients With Acute Graft-Versus-Host (GVHD) Disease
Number of patients with any grade of GVHD. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Acute GVHD usually happens within the first 3 months after transplant.
Time frame: Day 100 Post Transplant
Number of Patients With Transplant-Related Death (TRD)
Number of patients whose death is related to study treatment received. TRD is defined as the number of patients that die without prior relapse.
Time frame: 1 Year Post Transplant
Number of Patients With Complete Remission of Disease
Disease response will be measured by rate of leukemic clearance (clearance of blasts in blood at timepoint 0) and complete remission (less than 5% blasts and recovery of hematopoiesis).
Time frame: Day 100
Median Overall Survival
Average number of days the patients were alive after receiving UCB transplantation.
Time frame: Month 6
Number of Patients With Successful Natural Killer Expansion
Successful in vivo donor NK cell expansion will be defined as an absolute circulating donor-derived NK cell count of \>100 cells/μl.
Time frame: Day 72 Post Transplant
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