Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Human Papillomavirus-Associated Cancers
Condition: Cervical Cancer; Oropharyngeal Cancer; Vaginal Cancer; Anal Cancer; Penile Cancer
MeSH terms: Uterine Cervical Neoplasms; Anus Neoplasms; Oropharyngeal Neoplasms; Vaginal Neoplasms; Penile Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      The human papillomavirus (HPV) can cause a number of cancers, including cervical and throat
      cancers. The National Cancer Institute (NCI) Surgery Branch has developed an experimental
      therapy that involves taking white blood cells from patients' tumors, growing them in the
      laboratory in large numbers, and then giving the cells back to the patient. These cells are
      called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to
      over 200 patients with melanoma. Researchers want to know if TIL shrink s tumors in people
      with human papilloma virus (HPV)-related cancer. In this study, we are selecting a specific
      subset of white blood cells from the tumor that we think are the most effective in fighting
      tumors and will use only these cells in making the tumor fighting cells.

      Objective:

      The purpose of this study is to see if these specifically selected tumor fighting cells can
      cause HPV-related cancers to shrink and to see if this treatment is safe.

      Eligibility:

      - Adults age 18-66 with HPV-related cancer who have a tumor that can be safely removed.

      Design:

      Work up stage: Patients will be seen as an outpatient at the National Institutes of Health
      (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab
      tests, and other tests as needed.

      Surgery: If the patients meet all of the requirements for the study they will undergo surgery
      to remove a tumor that can be used to grow the TIL product.

      Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells.
      {Leukapheresis is a common procedure, which removes only the white blood cells from the
      patient.}

      Treatment: Once their cells have grown, the patients will be admitted to the hospital for the
      conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for
      about 4 weeks for the treatment.

      Follow up: Patients will return to the clinic for a physical exam, review of side effects,
      lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1
      year as long as their tumors are shrinking. Follow up visits will take up to 2 days.
    

Detailed description: 
      Background:

        -  Metastatic or locally advanced refractory/recurrent human papillomavirus
           (HPV)-associated malignancies (cervical, vulvar, vaginal, penile, anal, and
           oropharyngeal) are incurable and poorly palliated by standard therapies.

        -  Administration of autologous tumor infiltrating lymphocytes (TIL) generated from
           resected metastatic melanoma can induce objective long-term tumor responses.

        -  Young TIL can be generated from HPV-associated tumors.

      Objectives:

        -  To determine if autologous Young TIL infused in conjunction with high dose aldesleukin
           following a non-myeloablative lymphodepleting preparative regimen can mediate tumor
           regression in patients with metastatic or locally advanced refractory/recurrent
           HPV-associated cancer.

        -  To study immunologic correlates associated with Young TIL therapy for HPV-associated
           cancers.

        -  To determine the toxicity of this treatment regimen.

      Eligibility:

      - Patients greater than or equal to 18 years old with a pathologically confirmed diagnosis of
      metastatic or locally advanced refractory/recurrent HIPV-16+ or HPV-18+ human
      papillomavirus-associated cancer.

      Design:

        -  Patients will undergo biopsy or resection to obtain tumor for generation of autologous
           TIL cultures and autologous cancer cell lines.

        -  All patients will receive a non-myeloablative lymphocyte depleting preparative regimen
           of cyclophosphamide (60 mg/kg/day intravenous (IV)) on days -7 and -6 and fludarabine
           (25 mg/m(2)/day IV) on days -5 through -1.

        -  On day 0 patients will receive between 1 times 10 (9) to 2 times 10(11) young TIL and
           then begin high dose aldesleukin (720,000 IU/kg IV every 8 hours for up to 15 doses).

        -  Clinical and immunologic response will be evaluated about 4-6 weeks after TIL infusion.

        -  Initially, 18 evaluable patients will be enrolled in two cohorts; patients with cervical
           cancer and those with non- cervical cancer. For each cohort, if 0 to 2 of the 18
           patients experience a clinical response, then no further patients will be enrolled. If 3
           or more of the first 18 evaluable patients enrolled have a clinical response, then
           accrual will continue until a total of 35 evaluable patients have been enrolled in each
           cohort. Up to 73 patients may be enrolled over approximately 3-4 years.
    

Intervention name(s): Fludarabine; Cyclophosphamide; Young TIL; Aldesleukin
Intervention type(s): Drug; Drug; Biological; Drug
Intervention description(s): Fludarabine 25 mg/m(2)/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.; Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml in 5% dextrose in water (D5W) over 1 hr.; Cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes (between one and four days after the last dose of fludarabine).; Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over a 15 minute period approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
Other intervention name(s): Fludara; Cytoxan; TIL; Proleukin
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Immunotherapy; HPV-Associated Cancers; Cervical Cancer; Oropharyngeal Cancer; HPV Infection