This phase I/IIa trial studies the side effects and best dose of a type of specialized immune
cell (natural killer cell-like cytotoxic T-lymphocytes (CTLs) (nCTLs) and how well they work
when given with a vaccine (alpha-type-1 polarized dendritic cells) in treating patients with
stage II-IV ovarian, fallopian tube, or primary peritoneal cancer. nCTLs are immune cells
that are isolated from each patient?s blood and "taught" in the laboratory how to recognize
and eliminate tumor cells. These "educated" immune cells are then given back to the patient.
An alpha-type-1 polarized dendritic cell vaccine is another population of "educated" immune
cells that work to support the infused nCTLs. Giving nCTLS with a dendritic cell vaccine may
work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.
PRIMARY OBJECTIVES I. To evaluate the safety, tolerability, and feasibility of
intraperitoneal (i.p.) administration of autologous tumor loaded DC vaccines (alpha-type-1
polarized dendritic cell [alphaDC1]) combined with intradermally administered aDC1 .(Safety
[Phase I aspect]) II. To measure the intraperitoneal induction and persistence of aDCI
induced sensitized cytotoxic T Cells (CTLs), which express natural killer (NK) cell-like
features (nCTLs) and total CTLs following intraperitoneal administration of aDC1. (Local
Immunologic Efficacy [Phase II aspect])
SECONDARY OBJECTIVES I. To study the T cell populations generated that correlates with higher
anti-tumor responses.
EXPLORATORY OBJECTIVES I. To evaluate the progression-free survival and overall survival of
patients treated with this regimen.
OUTLINE: This is a phase I, dose-escalation study of nCTLs, followed by a phase IIa study.
Patients receive the alpha-type-1 polarized dendritic cell vaccine intradermally (ID) 2 weeks
before day 0, on day 0, and on day 28. Patients also receive nCTLs intraperitoneally (IP)
over 15-30 minutes on day 0. In the absence of unacceptable side effects, patients may
receive the alpha-type-1 polarized dendritic cell vaccine every 1-3 months at the discretion
of the physician.
After completion of study treatment, patients are followed up at 14 days, then at 6 and 12
months.
Inclusion Criteria:
- Eligible patients will be women with stages II-IV epithelial ovarian, fallopian tube,
or primary peritoneal carcinoma with no radiologic evidence of disease (NED) or
minimal disease burden after 1st line therapy. These patients would normally enter a
period of observation after standard management.
- Life expectancy > 6 months.
- Have been informed of other treatment options.
- Patients must be reasonable candidates for intraperitoneal (IP) port placement with no
prior evidence of persistent abdominal wall or intraperitoneal infections, renal
toxicity, or bowel obstruction or fistula.
- Patients must have documented available tumor: at least 1 cm of bulk tumor mass
collected at the time of primary or interval debulking surgery. The specimen may be
obtained on this protocol or as part of other Institutional Review Board (IRB)
approved tumor banking protocols.
- Patients should be free of active infection requiring antibiotics (with the exception
of uncomplicated urinary tract infection [UTI]).
- Must have adequate venous access for apheresis. (Pheresis catheter placement for cell
collection is allowed).
- Patient must agree to leukapheresis.
- Patients must agree to appropriate clinical monitoring to receive the study regimens.
- Absolute neutrophil count (ANC) greater than or equal to 1,000/uL.
- Platelets greater than or equal to 75,000/uL.
- Hemoglobin greater than or equal to 8.0 g/dL.
- Creatinine less than or equal to 2 x institutional upper limit normal (ULN).
- Bilirubin less than or equal to 1.5 x ULN.
- Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 3 x ULN.
- Alkaline phosphatase less than or equal to 3 x ULN.
- Participant or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure.
- Female subjects must either be of non-reproductive potential (i.e., post-menopausal by
history: >= 50 years old and no menses for >= 1 year without an alternative medical
cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
of bilateral oophorectomy) or must have a negative urine or serum pregnancy test
within 28 days of study treatment, confirmed prior to treatment.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of
0 or 1.
Exclusion Criteria:
- Metastatic disease to the central nervous system and any site above diaphragm.
- Other serious illnesses (e.g., serious infections requiring antibiotics [with the
exception of uncomplicated UTI], bleeding disorders).
- Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing
of study agent. Concomitant hormonal therapies are allowed.
- Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic
lupus erythematosus [SLE], ulcerative colitis, Crohn's Disease, multiple sclerosis
[MS], ankylosing spondylitis) requiring chronic use of steroids or other
immunosuppressives.
- Patients being chronically treated with immunosuppressive drugs such as cyclosporin,
adrenocorticotropic hormone (ACTH), or systemic chronic corticosteroids. NOTE: Recent
or current use of inhaled steroids is not exclusionary.
- Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g.,
interleukin 2, interferon alpha or gamma, granulocyte colony stimulating factors,
etc.) within 30 days prior to study entry.
- NOTE: Recent or current use of inhaled steroids is not exclusionary. If subjects
are prescribed a brief course of oral steroids, the use should be limited to less
than 7 days. Use of steroids before apheresis and immune assessment blood draws
will affect white blood cell function (wash out period of 1 week).
- Patients with a known immunodeficiency disease including cellular immunodeficiencies,
hypogammaglobulinemia or dysgammaglobulinemia; patients who have acquired, hereditary,
or congenital immunodeficiencies. Specific testing is not required, however may be
done as clinically indicated.
- Patients with uncontrolled diseases other than cancer may be excluded if after
consultation with PI and research team it is decided it might affect the treatment
efficacy or toxicity..
- Patients with tumors of low malignant potential, except ovarian pseudomyxoma or with
no peritoneal disease at initial diagnosis.
- Patients with a history of other invasive malignancies, with the exception of
nonmelanoma skin cancer, are excluded if there is any evidence of other malignancy
being present within the last three years. Patients are also excluded if their
previous cancer treatment contraindicates this protocol therapy.
- Evidence of current drug or alcohol abuse or psychiatric impairment, which in the
investigator's opinion will prevent completion of the protocol therapy or follow-up.
Specific testing is not required, however may be done as clinically indicated.
- Any condition that in the opinion of principal investigator (PI) would preclude
patient from successfully completing the protocol therapy or follow-up.
