Autologous T-Cells Combined With Autologous OC-DC Vaccine in Ovarian Cancer
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|ClinicalTrials.gov Identifier: NCT01312376|
Recruitment Status : Active, not recruiting
First Posted : March 10, 2011
Last Update Posted : July 19, 2016
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Carcinoma Fallopian Tube Cancer Primary Peritoneal Cancer||Biological: OC-DC vaccine Drug: Bevacizumab Drug: cyclophosphamide 300 mg/m2/d for 3 days Drug: fludarabine 30 mg/m2/d for 3 days Drug: ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells||Phase 1|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|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 Start Date :||March 2011|
|Actual Primary Completion Date :||October 2015|
- 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.
- Dose Limiting ToxicityDose limiting toxicity is defined as the occurrence of treatment-related adverse events.
- Tumor responseTumor response will be estimated by measures of tumor burden and survival.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01312376
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Janos Tanyi, MD||Abramson Cancer Center of the University of Pennsylvania|