At a glance
ClinicalIndex Comparison Record- ✓Measurable metastatic or refractory/recurrent HPV-16+ cancer confirmed by in situ hybridization or PCR-based testing
- ✓HLA-A*02 positive by low-resolution typing and HLA-A*02:01 by high-resolution typing
- ✓Prior receipt of first-line standard therapy or documented decline of standard therapy
- ✓Three or fewer brain metastases if treated with surgery or stereotactic radiosurgery; treated lesions must be clinically stable for ≥1 month before protocol treatment
- ✕Active systemic infections requiring anti-infective treatment
- ✕Primary immunodeficiency (e.g., Severe Combined Immunodeficiency Disease)
- ✕Concurrent opportunistic infections
- ✕Autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, pancreatitis, or systemic lupus erythematosus (hypothyroidism and vitiligo permitted)
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
A Phase I/II Trial of T Cell Receptor Gene Therapy Targeting HPV-16 E7 for HPV-Associated Cancers
In Brief
A Phase 2 clinical trial evaluating E7 TCR cells, Aldesleukin, and 19 other interventions for Papillomavirus Infections and 4 related conditions. Completed, enrolled 224 participants across 2 sites.
Detailed Summary
Background: Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have an 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 T cell receptor (TCR) cells, are then given back to the person to fight the cancer. Researchers want to see if this can help people. Objective: To determine a safe dose and efficacy of E7 TCR cells and whether these cells can help patients. Eligibility: Adults ages 18 and older with an HPV-16-associated cancer, including cervical, vulvar, vaginal, penile, anal, or oropharyngeal. Design: 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: Chemotherapy drugs E7 TCR cells Shots or injections to stimulate the 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.
Study Details
Timeline
Interventions
T cells genetically engineered with a T cell receptor (TCR) targeting human papillomavirus (HPV -16 E7 (E7 TCR) that display specific reactivity against human leukocyte antigen (HLA-A2+, HPV-16+ target cells.
Following cell infusion, the patient receives high-dose bolus aldesleukin, which is dosed to individual patient tolerance. Aldesleukin improves the survival of E7 T cell receptor (TCR) cells after infusion.
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Screening/Baseline. Follow-up (end of treatment).
Screening/Baseline. Following treatment (6 weeks post treatment preferred) and at disease progression only.
Screening/Baseline. Follow-up (end of treatment). 40 days (+/- 2 weeks) after cell infusion; additional visits as indicated.
Screening/Baseline.
Supportive medication for nausea/vomiting/anorexia. 0.01 mg/kg intravenous (IV) every(q) day as needed (prn).
Supportive medication for nausea/vomiting/anorexia. Ondansetron 10mg intravenous (IV) every(q) 8 hours(hr) as needed (prn).
Supportive medication for nausea/vomiting/anorexia. 1mg intravenous (IV) at 4-6 hours(h) as needed (prn).
Supportive medication for nausea/vomiting/anorexia. 25mg per rectum (PR) as needed (prn) or 10mg intravenous (IV) every(q) 6hours(h) prn.
Supportive medication for diarrhea. 2.5mg by mouth (po) every(q) 3 hours(h) as needed (prn).
Supportive medication for diarrhea. 25mcg by mouth (po) every(q) 3 hours(h) as needed (prn).
Supportive medication for diarrhea. 30-60mg by mouth (po) every(q) 4 hours(h) as needed (prn).
Supportive medication for diarrhea. 2mg by mouth (po) every(q) 3 hours(h) as needed (prn).
Supportive medication for fever. 50-75mg by mouth (po) every(q) 8 hours(h).
Supportive medication for fever. 650mg by mouth (po) every 4 hours (q) 4hr.
Supportive medication for pruritis. 25-50mg by mouth (po) every 4 hours (q) 4hr as needed (prn).
Supportive medication for pruritis. 10-20mg by mouth (po) every 6 hours(h), as needed (prn).
Supportive medication for chills. 25-50mg intravenous (IV) every 1 hour (q1hr), as needed (prn).