Clinical trial NCT00652899
Conditions: Fallopian Tube Cancer Ovarian Cancer Peritoneal Cavity Cancer
Keywords: recurrent ovarian epithelial cancer recurrent ovarian germ cell tumor stage IV ovarian epithelial cancer stage IV ovarian germ cell tumor fallopian tube cancer peritoneal cavity cancer
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2008-03-01; Completion date: 2009-08-01
Enrollment: 14 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: This group includes patients that received all chemotherapy, infusion of natural killer (NK) cells and total body irradiation per protocol.

1\. Allopurinol 300 mg by mouth daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post NK cell infusion. 2. Cyclophosphamide 60 mg/m\^2 on Days 4 and 5 preceding NK cell infusion. 3. Fludarabine phosphate 25 mg/m\^2 on Days 6 through 2 preceding NK cell infusion. 4. Radiation: total-body irradiation 200 cGy Day 1 preceding NK cell infusion. 5. Allogeneic natural killer cells- Given day 0 - dose of 1.5-8.0 \* 10\^7/kg. 6. Aldesleukin 10 million units 3 times/week for a total of 6 doses beginning Day 0. arm 2: This group includes patients that received chemotherapy and infusion of natural killer cells, but did not receive total body irradiation.

1\. Allopurinol 300 mg by mouth daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post NK cell infusion. 2. Cyclophosphamide 60 mg/m\^2 on Days 4 and 5 preceding NK cell infusion. 3. Fludarabine phosphate 25 mg/m\^2 on Days 6 through 2 preceding NK cell infusion. 4. Allogeneic natural killer cells- Given day 0 - dose of 1.5-8.0 \* 10\^7/kg. 5. Aldesleukin 10 million units 3 times/week for a total of 6 doses beginning Day 0.
Interventions: intervention 1: Allopurinol intervention 2: Cyclophosphamide intervention 3: Fludarabine phosphate intervention 4: total-body irradiation intervention 5: Allogeneic natural killer cells intervention 6: Aldesleukin
Intervention descriptions: intervention 1: 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. intervention 2: 60 mg/m\^2 on Days 4 and 5 preceding natural killer cell infusion. intervention 3: 25 mg/m\^2 on Days 6 through 2 preceding natural killer cell infusion. intervention 4: 200 cGy Day 1 preceding natural killer cell infusion. intervention 5: Given day 0 - dose of 1.5-8.0 \* 10\^7/kg intervention 6: 10 MU 3 times/week for a total of 6 doses beginning Day 0

Protocol documents: