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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01312376
Recruitment Status : Terminated
First Posted : March 10, 2011
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center at Penn Medicine

Tracking Information
First Submitted Date  ICMJE March 9, 2011
First Posted Date  ICMJE March 10, 2011
Last Update Posted Date April 24, 2020
Study Start Date  ICMJE March 2011
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
Dose Limiting Toxicity [ Time Frame: 5 Years ]
Dose limiting toxicity is defined as the occurrence of treatment-related adverse events.
Original Primary Outcome Measures  ICMJE
 (submitted: March 9, 2011)
Dose Limiting Toxicty
Dose limiting toxicty is defined as the occurrence of treatment-related adverse events.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
Tumor response [ Time Frame: 5 years ]
Tumor response will be estimated by measures of tumor burden and survival.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2011)
Tumor response
Tumor response will be estimated by measures of tumor burden and survival.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous T-Cells Combined With Autologous OC-DC Vaccine in Ovarian Cancer
Official Title  ICMJE 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
Brief Summary 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. (Funding Source - FDA OOPD)
Detailed Description

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. (Funding Source - FDA OOPD)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ovarian Carcinoma
  • Fallopian Tube Cancer
  • Primary Peritoneal Cancer
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 22, 2020)
18
Original Estimated Enrollment  ICMJE
 (submitted: March 9, 2011)
12
Actual Study Completion Date  ICMJE January 2019
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01312376
Other Study ID Numbers  ICMJE UPCC 26810, R01 FD 003520
FDA 00PD ( Other Grant/Funding Number: R01FD003520-04 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Abramson Cancer Center at Penn Medicine
Original Responsible Party George Coukos, MD, Abramson Cancer Center of the University of Pennsylvania
Current Study Sponsor  ICMJE Abramson Cancer Center at Penn Medicine
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Janos Tanyi, MD Abramson Cancer Center at Penn Medicine
PRS Account Abramson Cancer Center at Penn Medicine
Verification Date April 2020

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