Allogeneic Natural Killer (NK) Cells for Ovarian, Fallopian Tube, Peritoneal and Metastatic Breast Cancer
NCT ID: NCT01105650
Last Updated: 2017-12-28
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
13 participants
INTERVENTIONAL
2010-07-31
2014-04-30
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
Fludarabine
Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).
Cyclophosphamide
Administered intravenously, 60 mg/kg, days -5 and -4.
Cyclosporine
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Natural killer cells
Administered by infusion over less than 1 hour, no more than 8.0 x 10\^7 cells/kg will be given.
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).
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).
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.
Fludarabine
Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).
Cyclophosphamide
Administered intravenously, 60 mg/kg, days -5 and -4.
Cyclosporine
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Natural killer cells
Administered by infusion over less than 1 hour, no more than 8.0 x 10\^7 cells/kg will be given.
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).
Methylprednisolone
Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9
Methylprednisolone
Administered intravenously (IV) 1 mg/kg Days -2 to +9
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).
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.
Fludarabine
Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).
Cyclophosphamide
Administered intravenously, 60 mg/kg, days -5 and -4.
Cyclosporine
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Natural killer cells
Administered by infusion over less than 1 hour, no more than 8.0 x 10\^7 cells/kg will be given.
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).
Methylprednisolone
Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9
Methylprednisolone
Administered intravenously (IV) 1 mg/kg Days -2 to +9
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).
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.
Fludarabine
Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).
Cyclophosphamide
Administered intravenously, 60 mg/kg, days -5 and -4.
Cyclosporine
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Natural killer cells
Administered by infusion over less than 1 hour, no more than 8.0 x 10\^7 cells/kg will be given.
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).
Interventions
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Fludarabine
Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).
Cyclophosphamide
Administered intravenously, 60 mg/kg, days -5 and -4.
Cyclosporine
Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14
Natural killer cells
Administered by infusion over less than 1 hour, no more than 8.0 x 10\^7 cells/kg will be given.
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).
Methylprednisolone
Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9
Methylprednisolone
Administered intravenously (IV) 1 mg/kg Days -2 to +9
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 Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
* Active infection - subjects must be afebrile, off antibiotics, and with no uninvestigated radiologic lesions (infiltrates or lesions with negative cultures or biopsies) are allowed
18 Years
FEMALE
No
Sponsors
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Masonic Cancer Center, University of Minnesota
OTHER
Responsible Party
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Principal Investigators
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Melissa Geller, MD
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Locations
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Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Countries
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Other Identifiers
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MT2009-30
Identifier Type: OTHER
Identifier Source: secondary_id
1003M78876
Identifier Type: OTHER
Identifier Source: secondary_id
2009LS142
Identifier Type: -
Identifier Source: org_study_id