Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Mutated Neoantigens in People With Metastatic Cancer
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|ClinicalTrials.gov Identifier: NCT03412877|
Recruitment Status : Recruiting
First Posted : January 29, 2018
Last Update Posted : January 29, 2019
In gene transfer therapy, cells are taken from a person s tumor to isolate mutations. White blood cells are then taken from the person's body, changed with a type of virus to attack the tumor cells, and returned to the person.
To see if gene transfer therapy shrinks tumors.
People with certain metastatic cancer for which standard treatments have not worked
Participants will complete screening and stages 1-3 under another protocol. Screening includes:
Undergoing a biopsy or surgery at the NIH to obtain pieces of tumor in order to grow tumor cells
Blood, urine, heart, and lung tests
The study has 7 stages:
- Screening tests repeated over 1-2 weeks. Participants will have leukapheresis: Blood is removed by a needle in one arm. A machine removes white blood cells. The rest of the blood is returned by a needle in the other arm. An IV catheter will be placed in the chest.
- Care at home over 6-12 weeks.
- Stopping therapy for 4-6 weeks while their cells are changed in a lab.
- Hospital stay for 1 week to get chemotherapy by IV.
- Receiving changed cells by catheter. Then getting a drug over 1-5 days to help the cells live longer.
- Recover in the hospital for 1 2 weeks. Participants will get drugs and have blood and urine tests.
Participants will take an antibiotic and maybe an antiviral for at least 6 months after treatment. They will have repeat screening tests at visits every few months for the first year, every 6 months for the second year, then as determined.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Non-Small Cell Lung Cancer Ovarian Cancer Breast Cancer Gastrointestinal/Genitourinary Cancer||Drug: Cyclophosphamide Drug: Fludarabine Drug: Aldesleukin Biological: Individual Patient TCR-Transduced PBL||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||210 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Mutated Neoantigens in People With Metastatic Cancer|
|Actual Study Start Date :||September 6, 2018|
|Estimated Primary Completion Date :||March 23, 2027|
|Estimated Study Completion Date :||March 23, 2028|
Experimental: 1-Experimental Therapy
non-myeloablative lymphocyte depleting chemotherapy regimen of cyclophosphamide and fludarabine + Individual Patient TCR-Transduced PBL + high or low-dose aldesleukin
Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W with mesna 15 mg/kg/day over 1 hour x 2 days.
Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Aldesleukin 720,000 IU/kg IV over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 10 doses). Patients in cohort 3 may receive 72,000 IU/kg IV.
Biological: Individual Patient TCR-Transduced PBL
Day 0: Cells will be infused at a dose not to exceed 1.5E11 in 400 mL intravenously over 20-30 minutes or as clinically determined by an investigator for patient safety via non-filtered tubing, gently agitating the bag during infusion to prevent cell clumping.
- Response rate [ Time Frame: 6 and 12 weeks after cell infusion, then every 3 months x3, then every 6 months x 2 years, then per PI discretion ]Percentage of patients who have a clinical response to treatment (objective tumor regression)
- Phenotypic and functional characteristics of PBL [ Time Frame: 2-4 years post cell infusion ]
- In vivo survival of TCR gene-engineered cells [ Time Frame: 1 month post-treatment and then as indicated ]TCR and vector presence will be quantitated in PBMC samples using established PCR techniques
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): NCT03412877
|Contact: Ellen Bodurian||(866) 820-4505||IRC@nih.gov|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center 866-820-4505 email@example.com|
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute (NCI)|