RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, and total-body irradiation before a donor natural killer cell infusion helps stop the growth of tumor cells. It also helps stop the patient's immune system from rejecting the donor's natural killer cells. Aldesleukin may stimulate the natural killer cells to kill ovarian, fallopian tube, or primary peritoneal cancer cells. Treating the donor natural killer cells with aldesleukin may help the natural killer cells kill more tumor cells. PURPOSE: This phase II trial is studying how well giving laboratory-treated donor natural killer cells together with aldesleukin works when given after cyclophosphamide, fludarabine, and total-body irradiation in treating patients with recurrent and/or metastatic ovarian, fallopian tube, or primary peritoneal cancer.
OBJECTIVES: Primary * To evaluate the in vivo expansion of an infused allogeneic natural killer (NK) cell product following a preparative regimen comprising cyclophosphamide, fludarabine phosphate, and total-body irradiation in treating patients with recurrent and/or metastatic ovarian, fallopian tube, or primary peritoneal cancer. Secondary * To characterize the quantitative and qualitative toxicities of this treatment regimen. * To estimate disease response (complete or partial response) or clinical benefit (stable disease for \> 6 months) as measured by Response Evaluation Criteria in Solid Tumours (RECIST) criteria. * To estimate time to progression and overall survival. * To estimate the association between clinical response and donor/recipient KIR ligand matching status. Tertiary * To evaluate immune activation of the in vivo expanded haploidentical allogeneic NK cells and its effect on the immune system. OUTLINE: * Preparative regimen: Patients receive fludarabine phosphate IV on days 6 to 2 preceding natural killer (NK) cell infusion and cyclophosphamide IV on days 5 and 4 preceding NK cell infusion. Patients also undergo total-body irradiation on day 1 preceding NK cell infusion. * Allogeneic natural killer (NK) cell administration and aldesleukin: Patients receive aldesleukin-activated haploidentical allogeneic NK cells intravenously (IV) on day 0. Beginning 4-6 hours after allogeneic NK cell infusion, patients receive aldesleukin subcutaneously (SC) 3 times a week for 6 doses. Patients achieving any initial response (complete or partial response) or a clinical benefit (stable disease for \> 6 months) who progress after 6 months may receive 1 re-treatment course as above. Blood samples are collected at baseline, on days 0, 7, 14, and 28, and then at 2 and 3 months post NK cell infusion for cytokine measurements, immunophenotyping, functional analyses, and testing for persistence of donor cells. After completion of study treatment, patients are followed periodically for at least 1 year.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
All patients are to receive allopurinol 300 mg PO daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post natural killer cell infusion.
60 mg/m\^2 on Days 4 and 5 preceding natural killer cell infusion.
25 mg/m\^2 on Days 6 through 2 preceding natural killer cell infusion.
200 cGy Day 1 preceding natural killer cell infusion.
Given day 0 - dose of 1.5-8.0 \* 10\^7/kg
10 MU 3 times/week for a total of 6 doses beginning Day 0
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States
Number of Patients With In Vivo Expansion of Infused Allogeneic Natural Killer (NK) Cell Product
Detection of an absolute donor derived cell count of \> or = 100 cells/mL after NK cell infusion.
Time frame: Day 12-14
Number of Patients Per Disease Response
Response Evaluation Criteria in Solid Tumors (RECIST) criteria: Complete Response (CR)-Disappearance of all target lesions (TL); Partial Response (PR)-\< or = 30% decrease in the sum of the longest diameter (LD) of TL, reference baseline sum LD; Stable Disease (SD)-Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference the smallest sum LD since the treatment started; Progressive Disease (PD)- \< or = 20% increase in the sum of the LD of TL, reference the smallest sum LD recorded since treatment started or appearance of \< or = 1 new lesion.
Time frame: 1 Month After Natural Killer Cell Infusion (Day 30)
Median Number of Days to Progression
Median number of days from first date of treatment to date of disease progression (appearance of new metastatic lesions or objective tumor progression). Defined by computated tomography (CT) imaging based on Response Evaluation Criteria In Solid Tumors (RECIST): Progressive Disease (PD) \> or = 20% increase in sum of all target or any new lesions.
Time frame: From date of first treatment to disease progression
Median Overall Survival Number of Days Patients Alive After Treatment
Median number of days patients alive from date of treatment to date of death or date of last follow-up if censored.
Time frame: From first date on-study (treatment) to date of death
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.