Allogeneic Natural Killer (NK) Cells for Ovarian, Fallopian Tube, Peritoneal and Metastatic Breast Cancer

Brief Title

Allogeneic Natural Killer (NK) Cells for Ovarian, Fallopian Tube, Peritoneal and Metastatic Breast Cancer

Official Title

Lymphodepleting Chemotherapy and T-Cell Suppression Followed By Allogeneic Natural Killer Cells and IL-2 in Patients With Recurrent Ovarian, Fallopian Tube, Primary Peritoneal Cancer and Advanced Metastatic Breast Cancer (MT2009-30)

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.

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Response Rate

Secondary Outcome

 Time to Disease Progression

Condition

Ovarian Cancer

Intervention

Fludarabine

Study Arms / Comparison Groups

 Arm 1: CsA

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

July 2010

Completion Date

April 2014

Primary Completion Date

April 2014

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of recurrent ovarian cancer, fallopian tube, or primary peritoneal cancer
             that has failed or progressed after at least 2 prior salvage chemotherapy regimens
             (directed at recurrent/metastatic disease).

        OR

          -  Diagnosis of metastatic breast cancer (female or male) that has progressed on or
             failed at least one salvage chemotherapy regimen for metastatic disease and that meets
             the following disease specific related criteria:

               -  If estrogen receptor or progesterone receptor positive must have progressed on
                  prior hormonal therapy and/or

               -  if HER2-neu positive must have progressed on trastuzumab, lapatinib, or similar
                  agent

        Women with a history of both cancers are eligible for this study provided that they
        currently meet eligibility for one of the diseases. Women who have had another malignancy
        and have been disease free for at least 3 year, or with a history of completely resected
        non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.

          -  Measurable disease per disease specific Response Evaluation Criteria in Solid Tumors
             (RECIST) version 1.1 - patients with bone as their only site of disease will not be
             eligible.

          -  If history of brain metastases must be stable for at least 3 months after treatment -
             A brain computed tomography (CT) scan will only be required in subjects with known
             brain metastases at the time of enrollment or in subjects with clinical signs or
             symptoms suggestive of brain metastases.

          -  Available related HLA-haploidentical natural killer (NK) cell donor (by at least class
             I serologic typing at the A&B locus)

          -  Age 18 years or older

          -  Karnofsky performance status > or = 50%

          -  Adequate organ function as determined by the following criteria within 14 days of
             study enrollment

               -  Bone marrow: platelets > or = 80,000 x 10^9/L and hemoglobin > or = 9 g/dL,
                  unsupported by transfusions; absolute neutrophil count (ANC) > or = 1000 x
                  10^9/L, unsupported by growth colony stimulating factor (G-CSF) or
                  granulocyte-macrophage colony-stimulating factor (GM-CSF)

          -  Renal function: creatinine (Cr) < or = 2.0 mg/dL

          -  Liver function: Aspartate aminotransferase (AST), Alanine transaminase (ALT), total
             bilirubin, alkaline phosphatase < 5 times upper limit of institutional normal (ULN)

          -  Cardiac: Left ventricular ejection fraction >40% (within 28 days of treatment start)

          -  Pulmonary function: >50% corrected Carbon Monoxide Diffusing Capacity (DLCO) and
             Forced Expiratory Volume in One Second (FEV1), if presence of pleural effusion due to
             metastatic disease >40% corrected DLCO and FEV1 is acceptable (within 28 days of
             treatment start)

          -  Able to be off prednisone or other immunosuppressive medications for at least 3 days
             prior to Day 0

          -  At least 14 days must lapse between last prior anti-cancer treatment and 1st day of
             preparative regimen

          -  Voluntary written informed consent

        Exclusion Criteria:

          -  Pregnant or nursing - The agents used in this study may be teratogenic to a fetus and
             there is no information on the excretion of agents into breast milk. Participants of
             childbearing potential must have a blood test or urine study within 14 days prior to
             registration to rule out pregnancy and agree to use adequate birth control during
             study treatment

          -  Active infection - subjects must be afebrile, off antibiotics, and with no
             uninvestigated radiologic lesions (infiltrates or lesions with negative cultures or
             biopsies) are allowed

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Melissa Geller, MD, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT01105650

Organization ID

2009LS142

Secondary IDs

MT2009-30

Responsible Party

Sponsor

Study Sponsor

Masonic Cancer Center, University of Minnesota

Study Sponsor

Melissa Geller, MD, Principal Investigator, Masonic Cancer Center, University of Minnesota

Verification Date

December 2017