T-cell Receptor Gene Therapy Targeting HPV-16 E6 in Treating Patients with Metastatic, Recurrent, or Refractory HPV-Related Cancer
- Measurable metastatic or refractory/recurrent HPV-16+ cancer (determined by in situ hybridization [ISH] or a polymerase chain reaction [PCR]-based test)
- Patients must be human leukocyte antigen (HLA)-A*02:01-positive
- All patients must have received prior first line standard therapy or declined standard therapy, and have been either non-responders (progressive disease) or have recurred
- Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
- Able to understand and sign the informed consent document
- Willing to sign durable power of attorney
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Life expectancy of greater than 3 months
- Patients of both genders must be willing to practice birth control from the time of enrollment on this study up to 4 months after treatment; patients must be willing to undergo testing for HPV-16 prior to becoming pregnant
- Women of child bearing potential must have a negative pregnancy test
- Seronegative for human immunodeficiency virus (HIV) antibody
- Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody; if hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by reverse transcriptase (RT)-PCR and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative
- Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim
- White blood cell (WBC) >= 3000/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin > 8.0 g/dL
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< to 2.5 times the upper limit of normal
- Serum creatinine =< to 1.6 mg/dL
- Total bilirubin =< to 1.5 mg/dL, except in patients with Gilbert’s syndrome who must have a total bilirubin less than 3.0 mg/dL
- More than 4 weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen; note: patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria
- Women of childbearing potential who are pregnant or breastfeeding
- Active systemic infections (for e.g.: requiring anti-infective treatment), coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease
- Any form of primary immunodeficiency (such as severe combined immunodeficiency disease)
- Concurrent opportunistic infections
- Concurrent systemic steroid therapy
- History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine phosphate (fludarabine)
- History of coronary revascularization or ischemic symptoms
- Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested; the following patients will undergo cardiac evaluations * Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or * Age >= 60 years old
I. To determine a safe dose of administration of autologous T cells transduced with an anti-HPV-16 E6 T-cell receptor (TCR) and aldesleukin to patients following a nonmyeloablative but lymphodepleting preparative regimen.
II. To determine the objective tumor response rate (complete or partial response) and duration in patients with metastatic or recurrent/refractory HPV-16+ cancers treated with this regimen.
I. To determine the toxicity of this treatment regimen.
II. To study immunologic correlates associated with E6 TCR gene therapy for HPV16+ cancers.
OUTLINE: This is a phase I, dose-escalation study of autologous anti-HPV-16 E6 T-cell receptor gene-engineered peripheral blood lymphocytes followed by a phase II study.
PREPARATIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6 and fludarabine phosphate IV piggyback (IVPB) over 30 minutes on days -5 to -1.
AUTOLOGOUS T CELLS: Patients receive autologous anti-HPV-16 E6 T-cell receptor gene-engineered peripheral blood lymphocytes IV over 20-30 minutes on day 0.
ALDESLEUKIN: Beginning within 24 hours of T-cells infusion, patients receive aldesleukin IV over 15 minutes every 8 to 24 hours for up to 5 days.
After completion of study treatment, patients are followed up at 6 weeks, every month for 3 months, every 3 months for 9 months, every 6 months for 1 year, annually for 3 years, and then periodically thereafter for 10 years.
Trial Phase Phase I/II
Trial Type Treatment
NCI - Center for Cancer Research
Christian Sutter Hinrichs
- Primary ID 15-C-0005
- Secondary IDs NCI-2014-02319, RD-14-VIII-09, RD-14-VII-09, 337514, P141607, 1407-1331
- Clinicaltrials.gov ID NCT02280811