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
13
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