Autologous T-Cells Combined With Autologous OC-DC Vaccine in Ovarian Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01312376
First received: March 9, 2011
Last updated: October 10, 2014
Last verified: October 2014

March 9, 2011
October 10, 2014
March 2011
May 2014   (final data collection date for primary outcome measure)
Dose Limiting Toxicity [ Designated as safety issue: Yes ]
Dose limiting toxicity is defined as the occurrence of treatment-related adverse events.
Dose Limiting Toxicty [ Designated as safety issue: Yes ]
Dose limiting toxicty is defined as the occurrence of treatment-related adverse events.
Complete list of historical versions of study NCT01312376 on ClinicalTrials.gov Archive Site
Tumor response [ Designated as safety issue: Yes ]
Tumor response will be estimated by measures of tumor burden and survival.
Same as current
Not Provided
Not Provided
 
Autologous T-Cells Combined With Autologous OC-DC Vaccine in Ovarian Cancer
A Phase-1 Trial of Adoptive Transfer of Vaccine-Primed CD3/CD28-Costimulated Autologous T-Cells Combined With Vaccine Boost and Bevacizumab for Recurrent Ovarian Fallopian Tube or Primary Peritoneal Cancer Previously Vaccinated With Autologous Tumor Vaccine

This is a phase-I clinical trial to determine the feasibility and safety of Cyclophosphamide/Fludarabine Lymphodepletion and an immunomodulatory combination of Interferon-alpha Bevacizumab and Aspirin followed by adoptive transfer of vaccine-primed ex vivo CD3/CD28-costimulated peripheral blood autologous T cells and vaccination with whole tumor vaccine administered intradermally in combination with Bevacizumab in patients with recurrent ovarian cancer fallopian tube or primary peritoneal cancer

This is a phase-I clinical trial to determine the feasibility and safety of cyclophosphamide/fludarabine lymphodepletion and an immunomodulatory combination of Interferon-alpha (INF-a), Bevacizumab and Aspirin, followed by adoptive transfer of vaccine-primed, ex vivo CD3/CD28-costimulated peripheral blood autologous T-cells, and vaccination with whole tumor vaccine, administered intradermally in combination with Bevacizumab in patients with recurrent ovarian cancer, fallopian tube or primary peritoneal cancer who previously underwent induction vaccination with whole tumor vaccine.

Subjects will receive T-lymphocytes infusion at a dose of 20 billion ± 20% cells for all patients. Subjects who cant meet target dose level can still enroll but will be analyzed separately.

Before T-cell infusion, all subjects will undergo lymphodepletion with a single course of outpatient high-dose lymphodepleting chemotherapy with intravenous cyclophosphamide (300 mg/m2/d for 3 consecutive Days) and intravenous fludarabine (30 mg/m2/d for 3 consecutive Days on Days -5 to -3).

Subjects enrolled in this study will receive an immunomodulatory cycle of (Bevacizumab and Aspirin) ~14 Days before apheresis (if they do not have a frozen apheresis product from a previous collection) and another cycle between apheresis and T-cell infusion (approx. from Day -20 through Day -7, (+/- 5 Days)). The immunomodulatory cycle will consist of the following: intravenous 10 mg/kg Bevacizumab on Day -35, and Day -20 (+/- 5 Days), and 325 mg Enteric Coated Aspirin orally starting Day -35 for 14 Days and starting on Day -20 for 14 Days. They will also receive three subcutaneous injections of Interferon-alpha (Intron®a 2b) (INF-a) (subjects will have the option to self administer Interferon-alpha and they will be provided instructions) at a dose of 5 MIU on Days -3, -2 and -1. EX vivo CD3/CD28-costimulated lymphocytes will be infused ~1-2 Days after last Day of interferon-alpha treatment, ideally on Day 0.

All subjects will receive a dose of 5-10 million cells of OC-DC vaccine intradermally, or OC-L (2.5-5x106 oxidized tumor cells admixed with Montanide ISA 51 VG) 2-3 Days post T-cell infusion and on Day 16-18. Subjects will start receiving Bevacizumab at 15 mg/kg and vaccine (if available) starting Day 30 and every 3 weeks thereafter until end of study.

Interventional
Phase 1
Primary Purpose: Treatment
  • Ovarian Carcinoma
  • Fallopian Tube Cancer
  • Primary Peritoneal Cancer
  • Biological: OC-DC vaccine
    All subjects will receive a dose of 5-10 million cells of OC-DC intradermally
  • Drug: Bevacizumab
    Patients will start receiving Bevacizumab at 15 mg/kg starting Day 30 and every 4 weeks thereafter until end of study.
  • Drug: cyclophosphamide 300 mg/m2/d for 3 days
    All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous cyclophosphamide for 300 mg/m2/d for 3 days.
  • Drug: fludarabine 30 mg/m2/d for 3 days
    All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous fludarabine 30 mg/m2/d for 3 days
  • Drug: ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells
    All subjects will receive a single intravenous infusion of ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T-cells at the starting dose of 10-15 x 109 (10-15 billion) T-cells with escalating doses in cohort 2 and 3.
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
May 2014
May 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subjects who have received at least one vaccine under protocol UPCC-19809 or UPCC-29810.
  • ECOG performance status 0 or 1.
  • Subject has sufficient vaccine (2 vaccine doses are sufficient)
  • Must be at least 4 weeks post-operative
  • Blood coagulation parameters: PT such that international normalized ratio (INR) is less than1.5 (or an in-range INR, usually between 2 and 3, if a subject is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a PTT less than1.2 times the upper limit of normal.
  • Subject must be 18 years of age or older.
  • Life expectancy of greater than 4 months.
  • Normal organ and bone marrow function as defined by: Absolute neutrophil count greater than 1,000/microliter, Platelets greater than 100,000/microliter, Hematocrit greater than 30%, AST (SGOT)/ALT(SGPT) less than 2.5 X institutional upper limit of normal, Bilirubin less than 2.0 mg/dL unless secondary to bile duct blockage by tumor, and Creatinine less than 1.8 mg/dL

Exclusion Criteria:

  • Subjects who require or are likely to require more than a two-week course of corticosteroids for intercurrent illness. Subjects must complete therapy prior to enrollment. Topical corticosteroids should be stopped at least 2 weeks prior to enrollment and systemic corticosteroids should be stopped at least 4 weeks prior to enrollment.
  • Subjects with any acute infection that requires specific therapy. Acute therapy must have been completed at least seven days prior to study enrollment
  • Subjects with any underlying conditions, which would contraindicate therapy with, study treatment (or allergies to reagents used in this study).
  • Subjects with prior history or symptoms suggestive of partial or complete bowel obstruction.
  • Subjects receiving class III antiarrythmic medications.
  • Subjects receiving medications that might affect immune function. Additionally, H2 blockers are excluded, as are all antihistamines five days before and five days after each injection of study drug. NOTE: The following are exceptions: Proton pump Inhibitors (PPIs), NSAIDS including COX-2 inhibitors, acetaminophen.
  • Subjects who are allergic to Aspirin are excluded
  • Development of clinically significant co morbid disease that would contraindicate study therapy or confuse interpretation of study results.
  • Subjects with a History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess.
  • Subjects with evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01312376
UPCC 26810, FDA 00PD
Yes
Abramson Cancer Center of the University of Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Not Provided
Principal Investigator: Janos Tanyi, MD Abramson Cancer Center of the University of Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP