Clinical trial NCT00303667
Conditions: Acute Myelogenous Leukemia
Keywords: NK cells natural killer cells immunotherapy hematopoietic cell transplant acute myelogenous leukemia
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2005-01-01; Completion date: 2011-03-01
Enrollment: 50 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
OBJECTIVES:

Primary

* 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.

Secondary

* 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.

Correlative

* 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.

Arms: arm 1: Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin. arm 2: Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Interventions: intervention 1: aldesleukin intervention 2: natural killer cells intervention 3: cyclophosphamide intervention 4: fludarabine phosphate intervention 5: allogeneic hematopoietic stem cell transplantation intervention 6: total body irradiation intervention 7: Thymoglobulin intervention 8: Cyclosporin A intervention 9: cyclophosphamide intervention 10: fludarabine phosphate
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: Administered intravenously (IV) 50 mg/kg on Day -15 intervention 4: Administered intravenously (IV) 40 mg/m\^2 on Days -18 through -14 intervention 5: 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. intervention 6: Administered on Day -13, 200 cGy two times. intervention 7: intravenous (IV) 3 mg/kg on Day 0 (day of donor CD34 cell infusion) intervention 8: 1.5 mg/kg by mouth or intravenously for target dose range of 150-250; day -15 through day -8. intervention 9: Administered intravenously (IV) 50 mg/kg on Days -16 and -15 intervention 10: Administered intravenously (IV) 35 mg/m\^2 on Days -18 through -14

Protocol documents: