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

Primary Purpose

Ovarian Carcinoma, Fallopian Tube Cancer, Primary Peritoneal Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

OC-DC vaccine

Bevacizumab

cyclophosphamide 300 mg/m2/d for 3 days

fludarabine 30 mg/m2/d for 3 days

ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells

About this trial

This is an interventional treatment trial for Ovarian Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Abramson Cancer Center of the University of Pennsylvania

Outcomes

Primary Outcome Measures

Dose Limiting Toxicity

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

Secondary Outcome Measures

Tumor response

Tumor response will be estimated by measures of tumor burden and survival.

Full Information

NCT ID

NCT01312376

First Posted

March 9, 2011

Last Updated

April 22, 2020

Sponsor

Abramson Cancer Center at Penn Medicine

1. Study Identification

Unique Protocol Identification Number

NCT01312376

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Terminated

Study Start Date

March 2011 (undefined)

Primary Completion Date

October 2015 (Actual)

Study Completion Date

January 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Abramson Cancer Center at Penn Medicine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ovarian Carcinoma, Fallopian Tube Cancer, Primary Peritoneal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

OC-DC vaccine

Intervention Description

All subjects will receive a dose of 5-10 million cells of OC-DC intradermally

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Intervention Description

Patients will start receiving Bevacizumab at 15 mg/kg starting Day 30 and every 4 weeks thereafter until end of study.

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide 300 mg/m2/d for 3 days

Intervention Description

All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous cyclophosphamide for 300 mg/m2/d for 3 days.

Intervention Type

Drug

Intervention Name(s)

fludarabine 30 mg/m2/d for 3 days

Intervention Description

All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous fludarabine 30 mg/m2/d for 3 days

Intervention Type

Drug

Intervention Name(s)

ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells

Intervention Description

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.

Primary Outcome Measure Information:

Title

Dose Limiting Toxicity

Description

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

Time Frame

5 Years

Secondary Outcome Measure Information:

Title

Tumor response

Description

Tumor response will be estimated by measures of tumor burden and survival.

Time Frame

5 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janos Tanyi, MD

Organizational Affiliation

Abramson Cancer Center at Penn Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Abramson Cancer Center of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

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

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