Trial Information

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

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