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

This study has been terminated.
(Lack of NK cell expansion in 5/5 patients)
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01105650
First received: April 14, 2010
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Breast Cancer
Drug: Fludarabine
Drug: Cyclophosphamide
Drug: Cyclosporine
Biological: Natural killer cells
Drug: IL-2
Drug: Methylprednisolone
Drug: Interleukin-2
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Response Rate [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    Disease response demonstrated by using standard response criteria (RECIST) (Stable Disease (SD) + Partial Response (PR) + Complete Response (CR) after haploidentical donor NK cell infusion in patients with recurrent ovarian or breast cancer.


Secondary Outcome Measures:
  • Time to Disease Progression [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Time from study entry until progressive disease or data collection cutoff.

  • Overall Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Time from study entry until death or data collection cutoff.

  • Natural Killer (NK) Cell Expansion [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Evaluate the in vivo expansion of an infused CD3/CD19 depleted allogeneic donor NK cell product following a preparative regimen of cyclophosphamide, fludarabine and cyclosporine for the treatment of recurrent ovarian, fallopian tube and primary peritoneal cancer, and advanced metastatic breast cancer.


Enrollment: 13
Study Start Date: July 2010
Estimated Study Completion Date: February 2016
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: CsA
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.
Drug: Fludarabine
Administered intravenously, 25 mg/m^2, days -6 through -2 (5 days).
Other Name: Fludara
Drug: Cyclophosphamide
Administered intravenously, 60 mg/kg, days -5 and -4.
Other Name: Cytoxan
Drug: Cyclosporine
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Other Names:
  • Cyclosporine A
  • CsA
Biological: Natural killer cells
Administered by infusion over less than 1 hour, no more than 8.0 x 10^7 cells/kg will be given.
Drug: IL-2
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).
Other Name: Interleukin-2
Drug: Interleukin-2
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).
Other Name: IL-2
Experimental: Arm 2: CsA plus Methylprednisolone (10mg)
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.
Drug: Fludarabine
Administered intravenously, 25 mg/m^2, days -6 through -2 (5 days).
Other Name: Fludara
Drug: Cyclophosphamide
Administered intravenously, 60 mg/kg, days -5 and -4.
Other Name: Cytoxan
Drug: Cyclosporine
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Other Names:
  • Cyclosporine A
  • CsA
Biological: Natural killer cells
Administered by infusion over less than 1 hour, no more than 8.0 x 10^7 cells/kg will be given.
Drug: IL-2
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).
Other Name: Interleukin-2
Drug: Methylprednisolone
Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9
Other Name: Medrol
Drug: Methylprednisolone
Administered intravenously (IV) 1 mg/kg Days -2 to +9
Other Name: Medrol
Drug: Interleukin-2
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).
Other Name: IL-2
Experimental: Arm 3: CsA plus Methylprednisolone (1 mg)
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.
Drug: Fludarabine
Administered intravenously, 25 mg/m^2, days -6 through -2 (5 days).
Other Name: Fludara
Drug: Cyclophosphamide
Administered intravenously, 60 mg/kg, days -5 and -4.
Other Name: Cytoxan
Drug: Cyclosporine
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Other Names:
  • Cyclosporine A
  • CsA
Biological: Natural killer cells
Administered by infusion over less than 1 hour, no more than 8.0 x 10^7 cells/kg will be given.
Drug: IL-2
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).
Other Name: Interleukin-2
Drug: Methylprednisolone
Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9
Other Name: Medrol
Drug: Methylprednisolone
Administered intravenously (IV) 1 mg/kg Days -2 to +9
Other Name: Medrol
Drug: Interleukin-2
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).
Other Name: IL-2
Experimental: Arm 4: CsA minus Methylprednisolone
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.
Drug: Fludarabine
Administered intravenously, 25 mg/m^2, days -6 through -2 (5 days).
Other Name: Fludara
Drug: Cyclophosphamide
Administered intravenously, 60 mg/kg, days -5 and -4.
Other Name: Cytoxan
Drug: Cyclosporine
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Other Names:
  • Cyclosporine A
  • CsA
Biological: Natural killer cells
Administered by infusion over less than 1 hour, no more than 8.0 x 10^7 cells/kg will be given.
Drug: Interleukin-2
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).
Other Name: IL-2

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01105650

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Melissa Geller, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01105650     History of Changes
Other Study ID Numbers: 2009LS142, MT2009-30, 1003M78876
Study First Received: April 14, 2010
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
recurrent ovarian cancer
recurrent fallopian tube cancer
recurrent primary peritoneal cancer
refractory ovarian cancer
refractory fallopian tube cancer
refractory peritoneal cancer
metastatic breast cancer

Additional relevant MeSH terms:
Peritoneal Neoplasms
Ovarian Neoplasms
Fallopian Tube Neoplasms
Breast Neoplasms
Abdominal Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Breast Diseases
Skin Diseases
Cyclophosphamide
Fludarabine phosphate
Cyclosporins
Cyclosporine
Fludarabine
Interleukin-2
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone

ClinicalTrials.gov processed this record on September 16, 2014