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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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Female
Ovarian Cancer, Primary Peritoneal Cancer

Thank you

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


Inclusion Criteria:



- Previous participation in UPCC 11807 (A Phase I Clinical Trial of Autologous
Dendritic Cell Vaccine Loaded with Autologous Tumor Cell Lysate for Recurrent Ovarian
or Primary Peritoneal Cancer)

- PS < 2

- Subject must have tumor lysate sufficient to prepare at least 4 DCVax-L vaccines

- 18 years of age or older

- Life expectancy > 4 months

- Signed Informed Consent

- Normal organ and bone marrow function defined by:

- ANC ≥ 1,000/μl

- Platelets >100,000/μl

- AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal

- Bilirubin <2.0 mg/dL unless secondary to bile duct blockage by tumor

- Creatinine <1.5 X the upper limit of normal

Exclusion Criteria:

- Subjects with the following:

- known brain metastases

- renal insufficiency

- liver failure

- organ allograft

- known autoimmune/collagen vascular disorders

- pregnant or breast feeding

- non-healing wounds, ulcers, or bone fractures

- positive for serum anti-Yo (cdr2) antibodies

- uncontrolled hypertension

- Myocardial infarction or unstable angina within 6 months prior to registration

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Outcome Measure:

Disease status will be assessed with CT (or MRI) of chest/abdomen/pelvis at enrollment, after vaccine 2 and at the conclusion of the study . Rates of disease progression will be recorded at the time of study conclusion.

Outcome Time Frame:

Enrollment, 3 months after enrollment, End of study

Safety Issue:

No

Principal Investigator

George Coukos, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pennsylvania

Authority:

United States: Food and Drug Administration

Study ID:

UPCC 01808

NCT ID:

NCT00603460

Start Date:

January 2012

Completion Date:

March 2013

Related Keywords:

  • Ovarian Cancer
  • Primary Peritoneal Cancer
  • Ovarian Cancer
  • Peritoneal Cancer
  • Ovarian Neoplasms
  • Peritoneal Neoplasms

Name

Location

University of PennsylaniaPhiladelphia, Pennsylvania  19104