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

NCT00603460 | Withdrawn Phase 1 DMC

• 1 other identifier: UPCC 01808
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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:

• 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.

Conditions

Ovarian Cancer; Primary Peritoneal Cancer

Keywords

Ovarian Cancer; Peritoneal Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

A

ACTIVE COMPARATOR

Biological: DCVax-L and T Cells

B

ACTIVE COMPARATOR

Biological: DCVax-L and T Cells

Interventions

DCVax-L and T Cells BIOLOGICAL

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

Also known as: Cytoxan, Avastin, DCVax-L

A; B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Northwest Biotherapeutics: collaborator

Study Sites (1)

University of Pennsylania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Cyclophosphamide; Bevacizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• George Coukos, M.D., Ph.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2008
• First Posted: January 29, 2008
• Study Start: January 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: March 1, 2013
• Last Updated: May 2, 2017

Record last verified: 2017-04

Locations

US (1)