DCVax-L Vaccination With CD3/CD28 Costimulated Autologous T-Cells for Recurrent Ovarian or Primary Peritoneal Cancer
This study has been withdrawn prior to enrollment.
Sponsor:
University of Pennsylvania
Collaborator:
Northwest Biotherapeutics
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00603460
First received: January 16, 2008
Last updated: September 21, 2010
Last verified: September 2010
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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 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label |
| 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 |
Resource links provided by NLM:
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: | January 2012 |
| Estimated Study Completion Date: | March 2013 |
| Estimated Primary Completion Date: | January 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: A |
Biological: DCVax-L and T Cells
Arm A
Arm B
Other Names:
|
| Active Comparator: B |
Biological: DCVax-L and T Cells
Arm A
Arm B
Other Names:
|
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
No publications provided
| Responsible Party: | Carl H. June, M.D. / Professor, University of Philadelphia |
| ClinicalTrials.gov Identifier: | NCT00603460 History of Changes |
| Other Study ID Numbers: | UPCC 01808 |
| Study First Received: | January 16, 2008 |
| Last Updated: | September 21, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by University of Pennsylvania:
|
Ovarian Cancer Peritoneal Cancer |
Additional relevant MeSH terms:
|
Ovarian Neoplasms Peritoneal Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Abdominal Neoplasms Digestive System Neoplasms |
Digestive System Diseases Peritoneal Diseases Cyclophosphamide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |
ClinicalTrials.gov processed this record on May 22, 2013