NCT01312376

Autologous T-Cells Combined With Autologous OC-DC Vaccine in Ovarian Cancer

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

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Abramson Cancer Center at Penn Medicine · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase-I clinical trial to determine the feasibility and safety of Cyclophosphamide/Fludarabine Lymphodepletion and an immunomodulatory combination of Interferon-alpha 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. (Funding Source - FDA OOPD)

Detailed description

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 separately. 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. (Funding Source - FDA OOPD)

Conditions

• Ovarian Carcinoma
• Fallopian Tube Cancer
• Primary Peritoneal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	OC-DC vaccine	All subjects will receive a dose of 5-10 million cells of OC-DC intradermally
DRUG	Bevacizumab	Patients will start receiving Bevacizumab at 15 mg/kg starting Day 30 and every 4 weeks thereafter until end of study.
DRUG	cyclophosphamide 300 mg/m2/d for 3 days	All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous cyclophosphamide for 300 mg/m2/d for 3 days.
DRUG	fludarabine 30 mg/m2/d for 3 days	All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous fludarabine 30 mg/m2/d for 3 days
DRUG	ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells	All subjects will receive a single intravenous infusion of ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T-cells at the starting dose of 10-15 x 109 (10-15 billion) T-cells with escalating doses in cohort 2 and 3.

Timeline

• Start date: 2011-03-01
• Primary completion: 2015-10-01
• Completion: 2019-01-01
• First posted: 2011-03-10
• Last updated: 2020-04-24

Locations

1 site across 1 country: United States