Clinical trial NCT01105650
Conditions: Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer Breast Cancer
Keywords: recurrent ovarian cancer recurrent fallopian tube cancer recurrent primary peritoneal cancer refractory ovarian cancer refractory fallopian tube cancer refractory peritoneal cancer metastatic breast cancer
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2010-07-01; Completion date: 2014-04-01
Enrollment: 13 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a single center phase II trial designed to optimize a clinical platform of lymphodepleting chemotherapy and T-cell suppression to promote the persistence, function, and expansion of allogeneic natural killer (NK) cells in patients with recurrent ovarian, fallopian tube, primary peritoneal cancer and advanced metastatic breast cancer.

Detailed description:
The donor NK cells are infused on day 0, after a non-myeloablative preparative regimen of cyclophosphamide and fludarabine plus a cyclosporine A (CsA) based immunosuppressive therapy. Subcutaneous interleukin-2 (IL-2) is started the evening of the NK infusion and continued three times a week for 6 doses total.

Up to 4 sequential immunosuppressive platforms will be tested (Arms 1 and 2 are currently closed) to identify a platform where patients have the potential for successful NK cell expansion (defined as an absolute circulating donor derived NK cell count of \> 100 cells/μl 14 days after NK cell infusion). Once a clinical platform is determined, the platform will be expanded to a total of 18 patients. The primary goal of this extended phase is to obtain preliminary efficacy information.

Follow-up for disease response is for 1 year from the NK cell infusion, with the possibility of re-treatment for patients who experience at least a clinical benefit who progress after 6 months.

Arms: arm 1: Patients receiving Cyclosporine (CsA) and Natural Killer (NK) cells infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 6 doses given post NK cell infusion. arm 2: Patients receiving Cyclosporine (CsA), methylprednisolone and natural killer cells (NK) infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 6 doses given post NK cell infusion. arm 3: Patients receiving Cyclosporine (CsA), methylprednisolone and natural killer (NK) cells infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 6 doses given post NK cell infusion. arm 4: Patients receiving Cyclosporine (CsA), no methylprednisolone, eliminating IL-2 doses 4-6 and receiving Natural Killer (NK) cells infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 3 doses given post NK cell infusion.
Interventions: intervention 1: Fludarabine intervention 2: Cyclophosphamide intervention 3: Cyclosporine intervention 4: Natural killer cells intervention 5: IL-2 intervention 6: Methylprednisolone intervention 7: Methylprednisolone intervention 8: Interleukin-2
Intervention descriptions: intervention 1: Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days). intervention 2: Administered intravenously, 60 mg/kg, days -5 and -4. intervention 3: Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14 intervention 4: Administered by infusion over less than 1 hour, no more than 8.0 x 10\^7 cells/kg will be given. intervention 5: Will be given subcutaneously at 9 million units 3 times a week for a total of 6 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, will be given at 5 million units/m\^2 3 times per week for 6 doses). intervention 6: Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9 intervention 7: Administered intravenously (IV) 1 mg/kg Days -2 to +9 intervention 8: Will be given subcutaneously at million units 3 times a week for a total of 3 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, will be given at 3 million units/m\^2 3 times per week for 6 doses).

Protocol documents: