A Phase-1 Trial of Adoptive Transfer of Vaccine-Primed CD3/CD28-Costimulated Autologous T-Cells Combined With Vaccine Boost and Bevacizumab for Recurrent Ovarian Fallopian Tube or Primary Peritoneal Cancer Previously Vaccinated With Autologous Tumor Vaccine
This is a phase-I clinical trial to determine the feasibility and safety of
cyclophosphamide/fludarabine lymphodepletion and an immunomodulatory combination of
Interferon-alpha (INF-a), Bevacizumab and Aspirin, followed by adoptive transfer of
vaccine-primed, ex vivo CD3/CD28-costimulated peripheral blood autologous T-cells, and
vaccination with whole tumor vaccine, administered intradermally in combination with
Bevacizumab in patients with recurrent ovarian cancer, fallopian tube or primary peritoneal
cancer who previously underwent induction vaccination with whole tumor vaccine.
Subjects will receive T-lymphocytes infusion at a dose of 20 billion ± 20% cells for all
patients. Subjects who cant meet target dose level can still enroll but will be analyzed
Before T-cell infusion, all subjects will undergo lymphodepletion with a single course of
outpatient high-dose lymphodepleting chemotherapy with intravenous cyclophosphamide (300
mg/m2/d for 3 consecutive Days) and intravenous fludarabine (30 mg/m2/d for 3 consecutive
Days on Days -5 to -3).
Subjects enrolled in this study will receive an immunomodulatory cycle of (Bevacizumab and
Aspirin) ~14 Days before apheresis (if they do not have a frozen apheresis product from a
previous collection) and another cycle between apheresis and T-cell infusion (approx. from
Day -20 through Day -7, (+/- 5 Days)). The immunomodulatory cycle will consist of the
following: intravenous 10 mg/kg Bevacizumab on Day -35, and Day -20 (+/- 5 Days), and 325 mg
Enteric Coated Aspirin orally starting Day -35 for 14 Days and starting on Day -20 for 14
Days. They will also receive three subcutaneous injections of Interferon-alpha (Intron®a 2b)
(INF-a) (subjects will have the option to self administer Interferon-alpha and they will be
provided instructions) at a dose of 5 MIU on Days -3, -2 and -1. EX vivo
CD3/CD28-costimulated lymphocytes will be infused ~1-2 Days after last Day of
interferon-alpha treatment, ideally on Day 0.
All subjects will receive a dose of 5-10 million cells of OC-DC vaccine intradermally, or
OC-L (2.5-5x106 oxidized tumor cells admixed with Montanide ISA 51 VG) 2-3 Days post T-cell
infusion and on Day 16-18. Subjects will start receiving Bevacizumab at 15 mg/kg and vaccine
(if available) starting Day 30 and every 3 weeks thereafter until end of study.
Primary Purpose: Treatment
Dose Limiting Toxicity
Dose limiting toxicity is defined as the occurrence of treatment-related adverse events.
Janos Tanyi, MD
Abramson Cancer Center of the University of Pennsylvania
United States: Food and Drug Administration
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|