E7 TCR T Cells With or Without PD-1 Blockade for Human Papillomavirus-Associated Cancers
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|ClinicalTrials.gov Identifier: NCT02858310|
Recruitment Status : Recruiting
First Posted : August 8, 2016
Last Update Posted : March 12, 2018
Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have a HPV protein called E7 inside of their cells. In this new therapy, researchers take a person s blood, remove certain white blood cells, and insert genes that make them to target cancer cells that have the E7 protein. The genetically changed cells, called E7 TCR cells, are then given back to the person to fight the cancer. Researchers want to see if this can help people.
To determine a safe dose of E7 TCR cells and whether these cells can help patients.
Adults ages 18 66 with an HPV-16-associated cancer, including cervical, vulvar, vaginal, penile, anal, or oropharyngeal.
Participants will list all their medicines.
Participants will have many screening tests, including imaging procedures, heart and lung tests, and lab tests. They will have a large catheter inserted into a vein.
Participants will have leukapheresis. Blood will be removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm.
The cells will be changed in the lab.
Participants will stay in the hospital. Over several days, they will get:
E7 TCR cells
Cell growth factor
Shots or injections to stimulate blood cells
Participants will be monitored in the hospital up to 12 days. They will get support medicine and have blood and lab tests.
Participants will have a clinic visit about 40 days after cell infusion. They will have a physical exam, blood work, scans, and maybe x-rays.
Participants will have many follow-up visits with the same procedures. At some visits, they may undergo leukapheresis.
Participants will be followed for 15 years.
|Condition or disease||Intervention/treatment||Phase|
|Papillomavirus Infections Cervical Intraepithelial Neoplasia Carcinoma In Situ Vulvar Neoplasms Vulvar Diseases||Biological: E7 TCR Transduced PBL cells Drug: pembrolizumab Drug: aldesleukin Drug: fludarabine Drug: cyclophosphamide||Phase 1|
- Metastatic or refractory/recurrent human papillomavirus (HPV)-16+ cancers (cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers) are incurable and poorly palliated by standard therapies.
- HPV-16+ cancers constitutively express the HPV-16 E7 oncoprotein, which is absent from healthy human tissues.
- Administration of T cell receptor (TCR) gene engineered T cells can induce objective tumor responses in certain malignancies including HPV-16+ cancers.
- T cells genetically engineered with a TCR targeting HPV-16 E7 (E7 TCR) display specific reactivity against HLA-A2+, HPV-16+ target cells.
- Pembrolizumab is a monoclonal antibody that blocks PD-1, an inhibitory receptor on T cells, thereby preventing T cell inhibition. PD-1-blocking drugs have shown clinical activity in a variety of cancers.
- To determine a safe dose for E7 TCR cells plus aldesleukin with or without pembrolizumab for the treatment of metastatic HPV-16+ cancers.
- Patients greater than or equal to 18 years old and less than or equal to 66 years old with metastatic or refractory/recurrent HPV-16+ cancer.
- Prior first line systemic therapy is required unless the patient declines standard treatment.
- Patients must be HLA-A*02:01-positive.
- This is a phase I clinical trial that will test the safety of E7 TCR cells administered alone and in combination with pembrolizumab.
- All patients will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine followed by a single infusion of E7 TCR cells. Cell infusion will be followed by high-dose aldesleukin.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of T Cell Receptor Gene Therapy Targeting HPV-16 E7 With or Without PD-1 Blockade for HPV-Associated Cancers|
|Study Start Date :||August 4, 2016|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||January 1, 2026|
Experimental: dose escalation
subjects will be enrolled in cohorts of 3-6 subjects each per dose level of E7 TCR Transduced PBL cells
Biological: E7 TCR Transduced PBL cells
T cells genetically engineered with a TCR targeting HPV-16 E7 (E7 TCR) that display specific reactivity against HLA-A2+, HPV-16+ target cellsDrug: pembrolizumab
Pembrolizumab is a monoclonal antibody that blocks PD-1, an inhibitory receptor on T cells, thereby preventing T cell inhibition. PD-1-blocking drugs have shown clinical activity in a variety of cancers. Preclinical studies demonstrate that blockade of PD-1 can improve the efficacy of genetically engineered T cells for cancer treatmentDrug: aldesleukin
Following cell infusion the patient receives high-dose bolus aldesleukin, which is dosed to individual patient tolerance. Aldesleukin improves the survival of E7 TCR cells after infusion.Drug: fludarabine
Part of the non-myeloablative lymphocyte-depleting preparative regimen.Drug: cyclophosphamide
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
- Determine a safe dose for E7 TCR cells plus aldesleukin with or without pembrolizumab [ Time Frame: Phase I, 10 days after treatment ]Dose finding
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): NCT02858310
|Contact: Erin W Ferraro, R.N.||(833) firstname.lastname@example.org|
|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 National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Christian S Hinrichs, M.D.||National Cancer Institute (NCI)|