Treating Metastatic Cancer With Anti-VEGFR2 Gene Engineered CD8+ Lymphocytes
- One experimental treatment for certain types of cancer is cell therapy, which involves collecting lymphocytes (white blood cells) from an individual, growing the cells in the laboratory in large numbers, and then modifying the cells with a gene (anti-VEGFR2 gene) that prevents the growth of blood vessels that supply blood to tumors. Because this treatment is experimental, researchers are interested in determining the side effects and overall effectiveness of cell therapy using white blood cells modified with the anti-VEGFR2 gene as a treatment for aggressive cancer that has not responded to standard therapy.
- To determine the safety and effectiveness of cell therapy using anti-VEGFR2 gene modified tumor white blood cells to treat recurrent or relapsed cancer.
- Individuals greater than or equal to 18 years of age and less than or equal to 66 years of age who have been diagnosed with metastatic cancer that has not responded to or has relapsed after standard treatment.
- Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies.
- Cells for treatment will be collected during leukapheresis, which will separate the white blood cells and return the rest of the blood to the participant.
- Prior to the start of cell therapy, participants will have imaging procedures, heart and lung function tests, eye examinations, and blood and urine tests.
- For 7 days before the cell infusion, participants will be admitted for inpatient chemotherapy with cyclophosphamide and fludarabine to suppress the immune system in preparation for the cell therapy.
- Participants will receive the modified white blood cells as an infusion 1 to 4 days after the last dose of chemotherapy. The day after the infusion, participants will receive a dose of filgrastim to stimulate blood cell growth, and will begin to receive IL-2 (a drug that will help keep the modified white blood cells active) up to every 8 hours for 5 days.
- Participants will remain as inpatients for at least 5 to 10 days after the last IL-2 to recover from the treatment, and will be followed regularly after the treatment to study side effects and general effectiveness.
- Participants who initially respond to treatment but have a relapse may have one additional treatment using the same procedure.
Genetic: Anti-VEGFR2 CAR CD8 plus PBL
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Metastatic Cancer Using Lymphodepleting Conditioning Followed by Infusion of Anti-VEGFR2 Gene Engineered CD8+ Lymphocytes|
- Determine whether objective responses can be mediated in patients treated with the anti-VEGFR2 CAR engineered CD8+ PBL and low dose aldesleukin [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||October 2018|
|Estimated Primary Completion Date:||October 2018 (Final data collection date for primary outcome measure)|
Experimental: Single Arm
Patients will receive cells plus low dosealdesleukin - adoptic cell therapy
Genetic: Anti-VEGFR2 CAR CD8 plus PBL
Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophospamide and fludarabine followed by the administration of anti-VEGFR CAR CD8+ PBL and low dose aldesleukin. On day 0, cells will be infused in the Patient Care Unit over 20-30 minutes (Phase 1: 10e6- 3x10e10 cells and Phase 2: maximum tolerated dose of cells from Phase 1)Drug: Cyclophosphamide
Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W with mesna 15 mg/kg/day X 2 days over 1 hrDrug: Aldesleukin
Aldesleukin (based on total body weight) will be administered at a dose of 72,000 IU/kg as an intravenous bolus over a 15 minute period approximately every eight hours (+/- 1 hour) beginning within 24 hours of the cell infusion and continuing for up to 5 days (maximum 15 doses)Drug: Fludarabine
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01218867
|Contact: June Kryk, R.N.||(301) firstname.lastname@example.org|
|Contact: Steven A Rosenberg, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center 866-820-4505 firstname.lastname@example.org|
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute (NCI)|