E7 TCR Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer
Condition: Papillomavirus Infections; Oropharyngeal Neoplasms
MeSH terms: Papillomavirus Infections; Oropharyngeal Neoplasms
Intervention: E7 T-Cell Receptor (TCR)
Intervention description: The dose of E7 T-Cell Receptor (TCR) T cells will be 3 x 10^10 TCR+ T cells (unless fewer cells are generated) administered once.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: T Cell Receptor; Fludarabine; Cyclophosphamide; Immunotherapy; Aldesleukin

Summary:

      Background:

      The therapy used in this study is called E7 T-cell receptor (TCR) T cell therapy. This
      therapy is a type of treatment in which a participant's T cells (a type of immune system
      cell) are changed in the laboratory to attack cancer cells. This treatment might help people
      with human papillomavirus (HPV)-associated oropharyngeal cancer. Oropharyngeal cancer is a
      type of head and neck cancer that happens in the oropharynx (the part of the throat at the
      back of the mouth, including the soft palate, the base of the tongue, and the tonsils).
      Certain types of the HPV virus can cause this kind of cancer. This study is looking at
      treatments for cancer caused by HPV-16.

      Objective:

      The purpose of this study is to determine if E7 TCR T cells can be given safely without
      delaying standard treatment for HPV-16 associated oropharyngeal cancer. Standard treatment
      may be surgery or radiation therapy with chemotherapy.

      Eligibility: People ages 18 and older with Stage II or III HPV-16 associated oropharyngeal
      cancer

      Design:

      Participants will be screened with HLA typing (a blood test needed for eligibility) and HPV
      testing of the cancer tumor (to determine if the cancer is HPV-16 positive). A new biopsy may
      be needed if tumor from an outside location is not available for HPV testing. Eligible
      participants will come to the National Institutes of Health (NIH) campus to have a screening
      evaluation which will include physical exam, review of medical history and current
      medications, blood and heart tests, imaging (X-ray, computed tomography (CT) scan, magnetic
      resonance imaging (MRI) or positron emission tomography (PET) scan), and evaluation of
      participant's veins that are used for drawing blood.

      If the participant is eligible for the study based on the screening evaluation, they will
      have a baseline evaluation prior to receiving the experimental treatment. The baseline
      evaluation may include additional laboratory or imaging tests.

      Participants will have a large intravenous (IV) catheter inserted into a vein to undergo a
      procedure called leukapheresis. Leukapheresis is the removal of the blood by a machine to
      collect specific blood cells. The remaining blood is returned to the body. This procedure is
      needed to collect the cells that will be modified to target the cancer. These cells will be
      grown in the lab and given back to the participant through an IV. It takes 11-15 days to grow
      the cells.

      While the cells are growing, the participant will be admitted to the hospital about one week
      before cell infusion. They will receive 2 types of chemotherapy through an IV catheter over 5
      days. The main purpose of the chemotherapy is to make the cells more effective in fighting
      the cancer tumors. The cells will be given through an IV catheter 1-3 days after the last
      dose of chemotherapy. Within 24 hours after the cell infusion, participants will be given a
      cell growth factor called aldesleukin through an IV. Aldesleukin is thought to help the cells
      live longer in the participant s body. Participants will recover in the hospital until they
      are well enough to go home. This is usually about 7-12 days after the cell infusion or last
      dose of aldesleukin.

      Participants will have follow-up visits starting every 2 weeks after the date of cell
      infusion. These will be visits to monitor the safety of the treatment and to evaluate the
      response of the cancer to the treatment. These visits will continue if the cancer is
      shrinking. The participant will go back to their local cancer doctor for further care if the
      cancer stops shrinking, goes away completely or gets bigger.

      Participants will have blood drawn periodically to test if the cells have grown or changed.
      These blood tests will take place immediately before the cells are given, and then at 3, 6,
      12 months for the first year and then annually. These tests can be drawn locally and sent to
      the NIH. Participants will be asked to return to the NIH annually for a physical examination
      for 5 years after they receive the cells. After that time, participants will be asked to
      fill-out a questionnaire for the next ten years, for a total follow-up period of 15 years.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Histologically or cytologically confirmed stage II or stage III (American Joint
             Committee on Cancer (AJCC) 8th edition) oropharyngeal squamous cell carcinoma that has
             not been treated.

          -  Human papillomavirus 16 (HPV16)+ tumor and human leukocyte antigen A (HLA-A) 02:01+
             HLA type (HLA-A 02 is also acceptable for determination of eligibility).

          -  Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
             criteria.

          -  Patient age 18 and older. Because no dosing or adverse event data are currently
             available on the use of E7 T-cell receptor (TCR) T Cells in patients <18 years of age,
             children are excluded from this study. This reflects the age range of patients with
             the disease being studied.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          -  Women of child-bearing potential must have a negative pregnancy test because E7 TCR T
             Cells have unknown potential for teratogenic or abortifacient effects. Women of
             child-bearing potential are defined as all women who are not post-menopausal or who
             have not had a hysterectomy. Postmenopausal will be defined as women over the age of
             55 who have not had a menstrual period in at least 1 year.

          -  The effects of E7 TCR T Cells on the developing human fetus are unknown. For this
             reason and because the chemotherapy agents used in this trial are known to be
             teratogenic, women of child-bearing potential and men must agree to use adequate
             contraception (intrauterine device, hormonal or barrier method of birth control;
             abstinence; tubal ligation or vasectomy) prior to study entry and for four months
             after treatment. Should a woman become pregnant or suspect she is pregnant while she
             or her partner is participating in this study, she should inform her treating
             physician immediately.

          -  Seronegative for human immunodeficiency virus (HIV) antibody. The experimental
             treatment being evaluated in this protocol depends on an intact immune system.
             Patients who are HIV seropositive can have decreased immune-competence and thus be
             less responsive to the experimental treatment.

          -  Seronegative for hepatitis B antigen and hepatitis C antibody. If hepatitis C antibody
             test is positive, then the patient must be tested for the presence of antigen by
             Reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C virus
             ribonucleic acid (HCV RNA) negative.

          -  Must be willing to participate in Gene Therapy Long Term Followup Protocol, which will
             follow patients for up to 15 years per Food and Drug Administration (FDA)
             requirements.

          -  Patients must have organ and marrow function as defined below:

               -  leukocytes- greater than or equal to 3,000/mcL

               -  absolute neutrophil count- greater than or equal to 1,500/mcL

               -  platelets- greater than or equal to 100,000/mcL

               -  hemoglobin- greater than or equal to 9.0 g/dL

               -  total bilirubin- within normal institutional limits except in patients with
                  Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL

               -  Aspartate aminotransferase (AST) Serum glutamic oxaloacetic
                  transaminase(SGOT)/Alanine transaminase (ALT) Serum glutamic pyruvic
                  transaminase(SGPT)-Serum ALT/AST < 2.5 times upper limit of normal (ULN)

               -  creatinine clearance- Calculated creatinine clearance (CrCl) >50mL/min/1.73m(2)
                  for patients with creatinine levels above institutional normal (by the Chronic
                  Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)

          -  Ability of subject to understand and the willingness to sign a written informed
             consent document.

        EXCLUSION CRITERIA:

          -  Patients who are receiving any other investigational agents.

          -  History of severe allergic reactions attributed to compounds of similar chemical or
             biologic composition to agents used in study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations at the time of treatment that
             would limit compliance with study requirements.

          -  There is an unknown but potential risk for adverse events in nursing infants secondary
             to treatment of the mother with E7 TCR T Cells. For this reason, women may not
             breastfeed while receiving study treatment and for one year after the study treatment
             ends. These potential risks may also apply to other agents used in this study.

          -  Patients with any form of systemic immunodeficiency, including acquired deficiency
             such as human immunodeficiency virus (HIV) or primary immunodeficiency such as Severe
             Combined Immunodeficiency Disease, are ineligible. The experimental treatment being
             evaluated in this protocol depends on an intact immune system. Patients who have
             decreased immune competence may be less responsive to the treatment.

          -  Current use of immunosuppressive medication, EXCEPT for the following:

               -  Intranasal, inhaled, topical steroids, or local steroid injection (e.g.,
                  intra-articular injection);

               -  Systemic corticosteroids at physiologic doses less than equal to 10 mg/day of
                  prednisone or equivalent;

               -  Steroids as premedication for hypersensitivity reactions (e.g., computed
                  tomography (CT) scan premedication)

          -  Patients with autoimmune diseases such as Crohn's disease, ulcerative colitis,
             rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus
             erythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not
             exclusionary.

          -  Patients with a second active invasive cancer are not eligible if it may confound
             assessment of response to the current therapy.

          -  Patients who do not have a local physician to provide standard therapy post treatment.