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DCVax-L Vaccination With CD3/CD28 Costimulated Autologous T-Cells for Recurrent Ovarian or Primary Peritoneal Cancer
This study is not yet open for participant recruitment.
Verified by University of Pennsylvania, May 2008
Sponsors and Collaborators: University of Pennsylvania
Northwest Biotherapeutics
Information provided by: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00603460
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Primary Peritoneal Cancer
 Biological: DCVax-L and T Cells
 Phase I
Phase II

MedlinePlus related topics: Cancer Ovarian Cancer
Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Bevacizumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
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

Further study details as provided by University of Pennsylvania:

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. [ Time Frame: Enrollment, 3 months after enrollment, End of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 13
Study Start Date: May 2008
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Active Comparator 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
B: Active Comparator 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

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00603460

Locations
United States, Pennsylvania
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
  More Information

Responsible Party: University of Philadelphia ( Carl H. June, M.D. / Professor )
Study ID Numbers: UPCC 08108
Study First Received: January 16, 2008
Last Updated: May 7, 2008
ClinicalTrials.gov Identifier: NCT00603460  
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
Ovarian Cancer
Peritoneal Cancer

Study placed in the following topic categories:
Ovarian cancer
Ovarian Neoplasms
Digestive System Neoplasms
Gonadal Disorders
Genital Neoplasms, Female
Endocrine System Diseases
Urogenital Neoplasms
Bevacizumab
Fludarabine monophosphate
Cyclophosphamide
Ovarian Diseases
 Abdominal Neoplasms
Recurrence
Genital Diseases, Female
Digestive System Diseases
Peritoneal Diseases
Gastrointestinal Neoplasms
Fludarabine
Endocrinopathy
Peritoneal Neoplasms
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Adnexal Diseases
 Neoplasms
Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009



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