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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00603460
• Other study ID #: UPCC 01808
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: January 16, 2008
• Last updated: April 28, 2017
• Start date: January 2012
• Est. completion date: March 2013

Study information

• Verified date: April 2017
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
United States	University of Pennsylania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	Northwest Biotherapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Enrollment, 3 months after enrollment, End of study