DCVax-L Vaccination With CD3/CD28 Costimulated Autologous T-Cells for Recurrent Ovarian or Primary Peritoneal Cancer
Study Details
Study Description
Brief 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:
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ARM-IIA: maintenance DCVax-L vaccination, in combination with oral metronomic cyclophosphamide, or
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Description of treatment for Phase I:
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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.
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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.
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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.
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Ex vivo CD3/CD28-costimulated lymphocytes will be infused ~2 days after last day of fludarabine infusion.
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Patients will receive DCVax-L vaccine ~24-48 hrs after T cell infusion.
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Subjects will be contacted every 6 months for 5 years for survival.
Description of treatment for Phase II:
In ARM-IIA:
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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.
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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.
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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.
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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:
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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.
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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.
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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.
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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).
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Ex vivo CD3/CD28-costimulated lymphocytes will be infused ~2 days after last day of fludarabine infusion.
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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.
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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.
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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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: A
|
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
Other Names:
|
| Active Comparator: B
|
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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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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)
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PS < 2
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Subject must have tumor lysate sufficient to prepare at least 4 DCVax-L vaccines
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18 years of age or older
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Life expectancy > 4 months
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Signed Informed Consent
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Normal organ and bone marrow function defined by:
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ANC ≥ 1,000/μl
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Platelets >100,000/μl
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AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal
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Bilirubin <2.0 mg/dL unless secondary to bile duct blockage by tumor
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Creatinine <1.5 X the upper limit of normal
Exclusion Criteria:
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Subjects with the following:
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known brain metastases
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renal insufficiency
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liver failure
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organ allograft
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known autoimmune/collagen vascular disorders
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pregnant or breast feeding
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non-healing wounds, ulcers, or bone fractures
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positive for serum anti-Yo (cdr2) antibodies
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uncontrolled hypertension
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Myocardial infarction or unstable angina within 6 months prior to registration
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New York Heart Association (NYHA) Grade II or greater congestive heart failure
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pennsylania | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- University of Pennsylvania
- Northwest Biotherapeutics
Investigators
- Principal Investigator: George Coukos, M.D., Ph.D., University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UPCC 01808