Clinical Trials /

Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Human Papillomavirus-Associated Cancers

NCT01585428

Description:

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.

Related Conditions:
  • Cervical Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Immunotherapy</span> Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Human Papillomavirus-Associated Cancers

Title

  • Brief Title: Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Human Papillomavirus-Associated Cancers
  • Official Title: A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Aldesleukin for Human Papillomavirus-Associated Cancers
  • Clinical Trial IDs

    NCT ID: NCT01585428

    ORG ID: 120116

    NCI ID: 12-C-0116

    Trial Conditions

    Cervical Cancer

    Oropharyngeal Cancer

    Vaginal Cancer

    Anal Cancer

    Penile Cancer

    Trial Interventions

    Drug Synonyms Arms
    Fludarabine Cervical, NonCervica
    Cycolphosphamide Cervical, NonCervica
    Aldesleukin Cervical, NonCervica

    Trial Purpose

    Background:

    The human papillomavirus (HPV) can cause a number of cancers, including cervical and throat
    cancers. The 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 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 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/recurrentHIPV-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 IV) on days -7 and -6 and fludarabine (25 mg/m2/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 iwth
    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.

    Trial Arms

    Name Type Description Interventions
    Cervical Experimental Patients will receive a non-myeloablative lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by IV infusion of Young TIL plus high dose IV aldesleukin. Fludarabine, Cycolphosphamide, Aldesleukin
    NonCervica Experimental Patients will receive a non-myeloablative lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by IV infusion of Young TIL plus high dose IV aldesleukin Fludarabine, Cycolphosphamide, Aldesleukin

    Eligibility Criteria

    -INCLUSION CRITERIA:

    1. Measurable metastatic or locally advanced refractory/recurrent malignancies that are
    HPV-16 or HPV-18 high HPV positive by in situ hybridization (ISH) or polymerase chain
    reaction (PCR) or any cancer from the uterine cervix..

    2. All patients must have received at least one standard chemotherapy or
    chemoradiotherapy.

    3. 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.

    4. Greater than or equal to 18 years of age and less than or equal to age 70.

    5. Able to understand and sign the Informed Consent Document

    6. Clinical performance status of ECOG 0 or 1.

    7. Life expectancy of greater than three months

    8. Patients of both genders must be willing to practice birth control from the time of
    enrollment on this study and for up to four months after treatment.

    9. Serology:

    - Seronegative for 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 and more susceptible to its toxicities.)

    - Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody.
    If hepatitis C antibody test is positive, then patient must be tested for the
    presence of antigen by RT-PCR and be HCV RNA negative.

    10. Women of child bearing potential must have a negative pregnancy test because of the
    potentially dangerous effects of the treatment on the fetus.

    11. Hematology

    - Absolute neutrophil count greater than 1000/mm3 without the support of
    filgrastim

    - WBC greater than or equal to 3000/mm3

    - Platelet count greater than or equal too 100,000/mm3

    - Hemoglobin greater than 8.0 g/dl

    12. Chemistry:

    - Serum ALT/AST less than or equal to to 2.5 times the upper limit of normal

    - Serum creatinine less than or equal to to 1.6 mg/dl

    - Total bilirubin less that or equal to 1.5 mg/dl, except in patients with Gilbert
    s Syndrome who must have a total bilirubin less than 3.0 mg/dl.

    13. More than four weeks must have elapsed since any prior systemic therapy at the time
    the patient receives the preparative regimen, and patients toxicities must have
    recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

    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 in Section 2.1.1.

    14. More than four weeks must have elapsed since any prior radiation therapy.

    EXCLUSION CRITERIA:

    1. Women of child-bearing potential who are pregnant or breastfeeding because of the
    potentially dangerous effects of the preparative chemotherapy treatment on the fetus
    or infant.

    2. Active systemic infections, 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
    arrhythimas, obstructive or restrictive pulmonary disease.

    3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
    Disease).

    4. Concurrent opportunistic infections (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 experimental treatment and more susceptible
    to its toxicities).

    5. Concurrent systemic steroid therapy.

    6. History of severe immediate hypersensitivity reaction to any of the agents used in
    this study.

    7. History of coronary revascularization or ischemic symptoms.

    8. Any patient known to have an LVEF less than or equal to 45%.

    9. Documented LVEF of less than or equal to 45% tested in patients with i) clinically
    significant atrial and/or ventricular arrhythmias including but not limited to:
    atrial fibrillation, ventricular tachycardia, second or third degree heart block or
    ii) age greater than or equal 60 years old.

    10. Active Bleeding

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 70 Years

    Eligible Gender: Both

    Primary Outcome Measures

    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/recu...

    Secondary Outcome Measures

    Trial Keywords

    Immunotherapy

    HPV-Associated Cancers

    Cervical Cancer

    Oropharyngeal Cancer

    HPV Infection