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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).
Administered intravenously, 60 mg/kg, days -5 and -4.
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Administered by infusion over less than 1 hour, no more than 8.0 x 10\^7 cells/kg will be given.
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).
Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9
Administered intravenously (IV) 1 mg/kg Days -2 to +9
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).
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Response Rate
Response includes Complete Response (CR), Partial Response (PR), and Stable Disease (SD) as defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by CT or MRI. Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease.
Time frame: Month 3
Time to Disease Progression
Time from study entry until progressive disease or data collection cutoff.
Time frame: 1 Year
Number of Participants With Progressive Disease at One Year
Time frame: 1 Year
Overall Survival
Number of participants alive at 1 year.
Time frame: 1 Year
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