NCT00603460

DCVax-L Vaccination With CD3/CD28 Costimulated Autologous T-Cells for Recurrent Ovarian or Primary Peritoneal Cancer

A Phase-I/II Randomized Trial of Maintenance Vaccination Combined With Metronomic Cyclophosphamide w/wo Adoptive Transfer of CD3/CD28-CoStimulated T-Cells for Recurrent Ovarian or Primary Peritoneal Cancer Previously Vaccinated DCVax-L

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Pennsylvania · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Subjects with recurrent epithelial ovarian carcinoma or primary peritoneal cancer, who have previously undergone vaccination in clinical study UPCC-11807 with DCVax-L, an autologous vaccine with DC loaded in vitro with autologous tumor lysate. Phase I Subjects enrolled in this study will receive leukapheresis; followed by cyclophosphamide/fludarabine-induced lymphodepletion; followed by adoptive transfer of ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells; followed by a single DCVax-L vaccination, to establish feasibility and safety of this approach. Primary Objectives of Phase I To determine the feasibility and safety of administering vaccine-primed, ex vivo CD3/CD28-costimulated autologous peripheral blood T cells in combination with DCVax-L vaccination, following lymphodepletion with high dose cyclophosphamide/fludarabine. Phase II Twenty-two additional subjects will be randomized to receive either: * ARM-IIA: maintenance DCVax-L vaccination, in combination with oral metronomic cyclophosphamide, or * ARM-IIB: leukapheresis, followed by cyclophosphamide/fludarabine-induced lymphodepletion, followed by adoptive transfer of ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells, followed by maintenance DCVax-L vaccination, plus oral metronomic cyclophosphamide. Primary Objective of Phase II To assess the distribution of progression-free survival at 6 months for patients treated with maintenance DCVax-L vaccination plus oral metronomic cyclophosphamide as well as patients treated with ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells after lymphodepletion with high dose cyclophosphamide / fludarabine, followed by DCVax-L boost vaccination and metronomic oral cyclophosphamide.

Detailed description

Description of treatment for Phase I: * Patients will be offered, if medically indicated, tumor resection or needle aspiration of malignant effusion in order to make additional doses of DCVax-L vaccine. * If subjects have not received DCVax-L vaccination within the last 3-4 weeks, and if DCVax-L is available, subjects have the option of receiving one dose of DCVax-L after enrolment, to boost the frequency of vaccine-primed T cells. * Subjects will receive a single course of outpatient lymphodepleting chemotherapy with intravenous cyclophosphamide (300 mg/m2/d for 3 days) and intravenous fludarabine (30 mg/m2/d for 3 days) both administered on days 8 to 10. * Ex vivo CD3/CD28-costimulated lymphocytes will be infused \~2 days after last day of fludarabine infusion. * Patients will receive DCVax-L vaccine \~24-48 hrs after T cell infusion. * Subjects will be contacted every 6 months for 5 years for survival. Description of treatment for Phase II: In ARM-IIA: * Patients will be offered, if medically indicated, tumor resection or needle aspiration of malignant effusion in order to make additional doses of DCVax-L vaccine. * Subjects will receive intradermal vaccinations with DCVax-L every 8 weeks, for four cycles total. The first vaccine will be administered on day 0, which can be no sooner than 4 weeks from previous DCVax-L vaccination related to clinical study UPCC-11807. * Subjects will receive oral cyclophosphamide at metronomic schedule and dose (50 mg daily) every other week, starting \~3 weeks after DCVax-L in every vaccine cycle. * Patients will be offered (with the right to refuse) CT-guided needle biopsy or needle aspiration of malignant effusion after the second vaccine. In ARM-IIB: * Patients will be offered, if medically indicated, tumor resection or needle aspiration of malignant effusion in order to make additional doses of DCVax-L vaccine. * Subjects will undergo \~10-15 liter leukapheresis to derive vaccine-primed peripheral blood lymphocytes (PBL) on day 0. The apheresis material will be transferred to the Cell and Vaccine Facility at the University of Pennsylvania (Penn CVPF) for T cell manufacturing. * If subjects have not received DCVax-L vaccination within the last 3-4 weeks, and if DCVax-L is available, subjects have the option of receiving one dose of DCVax-L after enrolment, to boost the frequency of vaccine-primed T cells. * Subjects will receive a single course of outpatient lymphodepleting chemotherapy with intravenous cyclophosphamide (300 mg/m2/d for 3 days) and intravenous fludarabine (30 mg/m2/d for 3 days). * Ex vivo CD3/CD28-costimulated lymphocytes will be infused \~2 days after last day of fludarabine infusion. * Patients will receive DCVax-L vaccine boosts every 8 weeks for a total of four vaccines. The first DCVax-L will be given \~24-48 hrs after T cell infusion. * Following DCVax-L, subjects will receive oral cyclophosphamide at metronomic schedule and dose (50 mg daily) every other week x 3 cycles, starting \~3 weeks after DCVax-L in every vaccine cycle. * Patients will be offered (with the right to refuse) CT-guided needle biopsy or needle aspiration of malignant effusion \~1-2 weeks after the second vaccine

Conditions

• Ovarian Cancer
• Primary Peritoneal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	DCVax-L and T Cells	Arm A * Optional DCVax-L prior to chemotherapy * Apheresis * Chemotherapy for 3 days (IV fludarabine/cyclosphosphamide) * Infusion of activated T cells * DCVax-L vaccine * End of study visit Arm B * Optional DCVax-L prior to chemotherapy * Apheresis * Chemotherapy for 3 days (IV fludarabine/cyclosphosphamide) * Infusion of activated T cells * DCVax-L vaccine * Oral cyclophosphamide (one week on/one week off) for a total for a total of 6 weeks * End of study visit

Timeline

• Start date: 2012-01-01
• Primary completion: 2013-01-01
• Completion: 2013-03-01
• First posted: 2008-01-29
• Last updated: 2017-05-02

Locations

1 site across 1 country: United States