Ovarian CarcinomaPhase 1NCT01312376
Autologous T-Cells Combined With Autologous OC-DC Vaccine in Ovarian Cancer
A Phase 1 study testing OC-DC vaccine, Bevacizumab and cyclophosphamide 300 mg/m2/d for 3 days in people with Ovarian Carcinoma and Fallopian Tube Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Carcinoma, Fallopian Tube Cancer, Primary Peritoneal Cancer
- What is being tested?
- OC-DC vaccine, Bevacizumab and cyclophosphamide 300 mg/m2/d for 3 days
- Type of treatment
- Vaccines, Injection or infusion
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Jan 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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
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)
Read the 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)
- Being tested
- 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
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OC-DC vaccineBiological
All subjects will receive a dose of 5-10 million cells of OC-DC intradermally
BevacizumabDrug
Patients will start receiving Bevacizumab at 15 mg/kg starting Day 30 and every 4 weeks thereafter until end of study.
cyclophosphamide 300 mg/m2/d for 3 daysDrug
All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous cyclophosphamide for 300 mg/m2/d for 3 days.
fludarabine 30 mg/m2/d for 3 daysDrug
All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous fludarabine 30 mg/m2/d for 3 days
ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cellsDrug
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity
Dose limiting toxicity is defined as the occurrence of treatment-related adverse events.
Measured: 5 Years
Secondary outcomes (1)
Tumor response
Tumor response will be estimated by measures of tumor burden and survival.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2011 (estimated)
- Study startMar 2011
- Primary completionOct 2015
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian CarcinomaStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Janos Tanyi, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01312376
- Sponsor's protocol ID
- UPCC 26810, R01 FD 003520
- Other IDs
- FDA 00PD
- Status last verified
- Apr 2020
- First submitted
- 9 Mar 2011
- Last updated
- 24 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bobisse S, Bianchi V, Tanyi JL, Sarivalasis A, Missiaglia E, Petremand R, Benedetti F, Torigian DA, Genolet R, Barras D, Michel A, Mastroyannis SA, Zsiros E, Dangaj Laniti D, Tsourti Z, Stevenson BJ, Iseli C, Levine BL, Speiser DE, Gfeller D, Bassani-Sternberg M, Powell DJ Jr, June CH, Dafni U, Kandalaft LE, Harari A, Coukos G. A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer. Nat Cancer. 2023 Oct;4(10):1410-1417. doi: 10.1038/s43018-023-00623-x. Epub 2023 Sep 21.
PubMed 37735588
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01312376
- Acronym / sponsor ID
- UPCC 26810, R01 FD 003520
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Oct 2015 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 10 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OC-DC vaccineAll subjects will receive a dose of 5-10 million cells of OC-DC intradermally | Biological | – |
| BevacizumabPatients 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 daysAll 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 daysAll 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 cellsAll 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. | Drug | – |
Primary outcome
Dose Limiting Toxicity
Time frame: 5 Years
Dose limiting toxicity is defined as the occurrence of treatment-related adverse events.
1 secondary outcome
Tumor response
Time frame: 5 years
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2020.
- Derived from this study: PubMed 37735588Bobisse S, Bianchi V, Tanyi JL, Sarivalasis A, Missiaglia E, Petremand R, Benedetti F, Torigian DA, Genolet R, Barras D, Michel A, Mastroyannis SA, Zsiros E, Dangaj Laniti D, Tsourti Z, Stevenson BJ, Iseli C, Levine BL, Speiser DE, Gfeller D, Bassani-Sternberg M, Powell DJ Jr, June CH, Dafni U, Kandalaft LE, Harari A, Coukos G. A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer. Nat Cancer. 2023 Oct;4(10):1410-1417. doi: 10.1038/s43018-023-00623-x. Epub 2023 Sep 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janos Tanyi, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OC-DC vaccine, Bevacizumab and cyclophosphamide 300 mg/m2/d for 3 days in people with Ovarian Carcinoma and Fallopian Tube Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (time frame: 5 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01312376, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2020.