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Patients receive cyclophosphamide, fludarabine phosphate, total-body irradiation, T cell depleted umbilical cord blood transplantation (UCBT), followed by interleukin-2 (IL-2, aldesleukin) every other day beginning day +3 for a total of 6 doses and again on day +60 every other day for 6 doses.

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.

aldesleukin

60 mg/kg over 1 hour intravenously (IV) on days -7 and -6.

cyclophosphamide

25 mg/m\^2 intravenously (IV) over 1 hour on days -7 through -5.

fludarabine phosphate

On day 0, transplantation will occur with double T-cell depleted (TCD) umbilical cord blood (UCB) units

umbilical cord blood transplantation

administered on days -5 through -2; 330 cGy daily

total-body irradiation

Michael R. Verneris, MD

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.

Chemotherapy, Total-Body Irradiation, Donor Natural Killer Cell Infusion, Aldesleukin, and UCB Transplant in Treating Patients With Relapsed or Refractory AML

Haploidentical Donor NK Cell Adoptive Therapy and Double T Cell Depleted Umbilical Cord Blood Transplantation With Post-Transplant IL-2 Immune Therapy For Refractory Acute Myeloid Leukemia

Number of patient with absolute neutrophils \>500\*10\^8/kg by 42 days post transplant.

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.

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.

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.

Number of patients whose death is related to study treatment received. TRD is defined as the number of patients that die without prior relapse.

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).

Average number of days the patients were alive after receiving UCB transplantation.

Successful in vivo donor NK cell expansion will be defined as an absolute circulating donor-derived NK cell count of \>100 cells/μl.

Masonic Cancer Center, University of Minnesota

Patients that receive myeloablative preparative regimen (allopurinol 300 mg by mouth Day -8 through +14; fludarabine 25 mg/m\^2 intravenously on days -7 through -5; cyclophosphamide 60 mg/kg intravenously on days -7 and -6; total body irradiation 165 cGy\*2 on days -4 through -2), 2 units T cell depleted umbilical cord blood transplant on day 0, followed by IL-2 every other day beginning day +3 and day +60 for a total of 6 doses.

Patients Receiving Double Umbilical Cord Blood Transplant

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Quantitative, phenotypic and functional assessment of the in vivo expanded UCB-derived NK cells on Day 72 were not performed. Patients were not well enough to provide research samples.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Chemotherapy, Total-Body Irradiation, Donor Natural Killer Cell Infusion, Aldesleukin, and UCB Transplant in Treating Patients With Relapsed or Refractory AML	NCT00871689	Leukemia	aldesleukin cyclophosphamid... fludarabine pho... umbilical cord ... total-body irra...	- 45 Years	Masonic Cancer Center, University of Minnesota
Chemotherapy, Total-Body Irradiation, Donor Natural Killer Cell Infusion, Aldesleukin, and UCB Transplant in Treating Patients With Relapsed or Refractory AML	NCT00871689	Leukemia	aldesleukin cyclophosphamid... fludarabine pho... umbilical cord ... total-body irra...	- 45 Years	Masonic Cancer Center, University of Minnesota

Spots Global Cancer Trial Database for childhood acute myeloid leukemia with t(16;16)(p13;q22)