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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

Phase 1
18 Years
Open (Enrolling)
Ovarian Carcinoma, Fallopian Tube Cancer, Primary Peritoneal Cancer

Thank you

Trial Information

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 (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

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.

Inclusion Criteria:

- Subjects who have received at least one vaccine under protocol UPCC-19809 or

- 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

- 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

- 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.

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Dose Limiting Toxicity

Outcome Description:

Dose limiting toxicity is defined as the occurrence of treatment-related adverse events.

Safety Issue:


Principal Investigator

Janos Tanyi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania


United States: Food and Drug Administration

Study ID:

UPCC 26810



Start Date:

March 2011

Completion Date:

March 2016

Related Keywords:

  • Ovarian Carcinoma
  • Fallopian Tube Cancer
  • Primary Peritoneal Cancer
  • Carcinoma
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms



Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283