Clinical trial NCT01370213
Conditions: Acute Myeloid Leukemia Myelodysplastic Syndrome
Keywords: non-myeloablative haploidentical transplant hematopoietic cell transplant natural killer cells adoptive cellular therapy
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2011-09-01; Completion date: 2017-04-01
Enrollment: 25 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase II multi-institutional therapeutic study of NK-cell based nonmyeloablative haploidentical transplantation for the treatment of high-risk acute myeloid diseases. Enrollment will use a two-stage design. Stage 1 will enroll 15 patients unless an early stopping rule is met. If 9 or more of these first 15 patients achieve leukemia free neutrophil engraftment at day +28 accrual will move to stage 2. In stage 2, an additional 28 patients will be enrolled for a total of 43 patients. Patients will be followed for disease response for 2 years.

Detailed description:
A reduced intensity conditioning using Fludara, Cytoxan, and irradiation will start on day -22, followed by infusion of donor NK (natural killer) cells on day-17, 6 doses of interleukin-2 (IL-2) to promote NK expansion (day -17 to day -7), 2 doses of ATG for additional immunosuppression to promote engraftment (day -5 to -4), and infusion of a TCR α/β-depleted same donor graft on day 0.

Arms: arm 1: Patients with high risk acute myeloid disease treated with preparative regimen including Fludara, Cytoxan and total body irradiation followed by haploidentical donor NK cells, Interleukin-2, rabbit anti-thymocyte globulin, and filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor. arm 2: Patients with high risk acute myeloid disease treated with preparative regimen including Fludara, Cytoxan and total body irradiation followed by haploidentical donor NK cells, Interleukin-2, rabbit anti-thymocyte globulin, and same donor TCR α/β-depleted cells infusion.
Interventions: intervention 1: Preparative Regimen intervention 2: NK Cells intervention 3: Interleukin-2 intervention 4: CD34 Graft/Anti-thymocyte globulin intervention 5: Donor TCR α/β-depleted Graft/ATG
Intervention descriptions: intervention 1: Preparative Regimen:

1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant, 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pretransplant, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pretransplant, intervention 2: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pretransplant. intervention 3: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion intervention 4: Single donor filgrastim mobilized CD34+ selected peripheral blood stem cell graft (minimum cell dose of 5 x 10\^6/kg) on day 0. Rabbit anti-thymocyte globulin (ATG) will be administered on day -1 (0.5 mg/kg) and day +1 and +2 (2.5 mg/kg) pretransplant per institutional guidelines. ATG dosing not identical for all patients. intervention 5: Single donor TCR α/β-depleted filgrastim-mobilized peripheral blood stem cells (PBSC) graft (minimum cell dose of 5 x 10\^6/kg) on day 0. ATG will be administered on days -6 and -5 (3mg/kg) for most patients.

Protocol documents: