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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given ID
Given IP
Roswell Park Cancer Institute
Buffalo, New York, United States
Incidence of adverse events as assessed by Cancer Therapy Evaluation Program (CTEP) version 4 of the Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: Up to 12 months
Dose-limiting toxicities (DLT) assessed by CTCAE version 5
Will be used in the estimation of the maximum tolerated dose (MTD) and the accompanying of the dose escalation decisions. However, no formal analyses of DLTs are planned.
Time frame: Up to 14 days after intraperitoneal (IP) infusion of nCTLs
Change in immune response
Change in immune response will be measured by the increase in the number of CD3+CD8+NKG2D (high) natural killer cell-like cytotoxic T-lymphocyte (CTLs) (nCTLs) and the increase in total CD3+CD8+ CTLs recovered in the peritoneal washes with evaluation on day 0 versus day 2. The analysis will consist of an analysis-of-covariance (ANCOVA) for the outcome of post-pre ACT treatment cell count with a factor for dose and sampling time 48 hrs +/- 24 hrs.
Time frame: From baseline (day 0) to day 2 (48 hours after adoptive cell therapy [ACT]) administration
Persistence of nCTLs after their adoptive transfer
At day 0 will obtain peritoneal material (outflow and washes) directly before i.p. infusion of nCTLs, as well as day 2 (48 hours +/- 24 hours), day 7 (+/- 2 days), 2 weeks (14 days +/- 2 days) and 4 weeks (28 days +/- 3 days) later.
Time frame: Up to 4 weeks
T cell populations and higher anti-tumor responses
Will estimate the half-life of CD3/CD8/NKG2D (triple-positive nCTLs) cell counts and longitudinal changes CD3/CD8 cell counts (double-positive CTLs, which include both nCTLs and additional CTLs newly recruited CTLs from the circulation) cell counts as a function of dose and time. A nonlinear regression model with a random effect for subject (population pharmacokinetics \[PK\]) will be fit to a one-compartment kinetics first-order absorption model per dose level.
Time frame: Up to 4 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.