Clinical Trials /

Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4

NCT02027935

Description:

The goal of this clinical research study is to learn about the safety of giving CD8+T cells with ipilimumab, cyclophosphamide, and IL-2 (aldesleukin). Researchers also want to learn if this combination can help to control metastatic melanoma (melanoma that has spread). This study is divided into 2 parts: leukapheresis and treatment. In the leukapheresis part, blood cells will be collected from you to be made into modified CD8+T cells and given back to you in the treatment part. CD8+T cells are a type of white blood cell. Researchers grow the T cells in the laboratory, and they are designed to find melanoma cancer cells and may kill them. Ipilimumab and aldesleukin are designed to increase the immune system's ability to fight cancer. Cyclophosphamide will be used at a very low dose to weaken the body's natural defense against the T-cell transplant, so that the transplanted T-cells have a chance to grow and multiply. This is an investigational study. CD8+T cells are not FDA approved or commercially available. They are currently being used for research purposes only. Cyclophosphamide, ipilimumab, and aldesleukin are FDA approved and commercially available for the way they are being used in this study. Up to 30 participants will be enrolled in this multicenter study. Up to 20 will take part at MD Anderson.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Cellular <span class="go-doc-concept go-doc-intervention">Adoptive Immunotherapy</span> Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4

Title

  • Brief Title: Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4
  • Official Title: Phase II Study of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4 for Patients With Metastatic Melanoma
  • Clinical Trial IDs

    NCT ID: NCT02027935

    ORG ID: 2012-1055

    NCI ID: R1301

    Trial Conditions

    Melanoma

    Trial Interventions

    Drug Synonyms Arms
    Cyclophosphamide Cytoxan, Neosar CD8+ T Cells + Cyclophosphamide + Interleukin-2 + Ipilimumab
    Interleukin-2 Aldesleukin, IL-2, Proleukin CD8+ T Cells + Cyclophosphamide + Interleukin-2 + Ipilimumab
    Ipilimumab Yervoy, BMS-734016, MDX010 CD8+ T Cells + Cyclophosphamide + Interleukin-2 + Ipilimumab

    Trial Purpose

    Objectives:

    Primary Objectives:

    Evaluate the safety and efficacy of adoptively transferred CTL targeting melanoma tumors
    combined with anti-CTLA4.

    Secondary Objective:

    Evaluate the influence of anti-CTLA4 on the duration of in vivo persistence and anti-tumor
    efficacy achieved following adoptive transfer of antigen-specific CTL

    Evaluate the influence of anti-CTLA4 on the induction of T cells to non-targeted
    tumor-associated antigens (antigen-spreading) following adoptive transfer antigen-specific
    CTL, and the correlation of these responses with clinical outcome.

    Detailed Description

    You will have a leukapheresis procedure to collect blood cells so they can be separated and
    grown as CD8+T cells. For this procedure, you will need to stay seated in a chair and keep
    both arms still for about 3 hours. Blood will be drawn from 1 arm, the white blood cells
    will be separated from the rest of the blood cells in the leukapheresis machine, and the red
    cells, platelets, and plasma (liquid part of the blood) will be returned through your other
    arm.

    The white blood cells will be collected into a sterile bag. A steady stream of blood will
    flow from you into the leukapheresis machine and back into you through tubing attached to
    the catheters and needles in your arms. Citrate will be added to the blood as it enters the
    machine in order to lower the risk of your blood clotting in the machine.

    If you cannot have a leukapheresis procedure, blood (about 2/3 cups each time) will be drawn
    2-4 times to collect blood cells so they can be separated and grown as CD8+T cells.
    Researchers may use the white blood cells that were previously collected from you when you
    consented to take part in Protocol PA14-0138.

    If enough white blood cells cannot be collected, you will not be enrolled in the study.

    On the day of your leukapheresis visit:

    - Blood (about 1 tablespoons) will be drawn for routine tests.

    Once the T-cells collected during leukapheresis are modified in the laboratory and prepared
    for your treatment, you will be screened again. You will be given a second consent form that
    will describe this additional screening, as well as the study treatment.

    There will be at least 3-4 months between the leukapheresis and the time when the CD8+T
    cells are ready to give back to you. You may receive other therapies during this time as
    long as you do not receive another treatment within 3 weeks before the CD8+T cell dose.
    Please ask your doctor about your options during this 3-4 month period.

    This is an investigational study. CD8+T cells are not FDA approved or commercially
    available. They are currently being used for research purposes only.

    Up to 30 participants will be enrolled in this multicenter study. Up to 20 will take part at
    MD Anderson.

    Part 2 - Treatment:

    Study Drug Administration:

    If you agree to take part in this study, you will receive cyclophosphamide by vein over
    about 30-60 minutes on Day -2 (2 days before you receive the CD8+ T cells). If the doctor
    thinks it is needed, you will be given standard drugs to help decrease the risk of side
    effects. You may ask the study staff for information about how the drug is given and its
    risks.

    On Day 0, you will receive the CD8+ T cells by vein over about 30-60 minutes. You will stay
    in the hospital overnight after the dose.

    Starting within 6 hours after the CD8+T cell infusion and then 2 times a day after that for
    14 days, you will give aldesleukin as an injection into your skin around your abdomen. You
    will be taught how to give yourself these injections.

    On Days 1, 22, 43, and 64, you will receive ipilimumab by vein over about 90 minutes.

    Study Visits:

    On Day -2:

    - You will have a physical exam.

    - Blood (about 1 tablespoon) will be drawn for routine tests. This routine blood draw
    will include a pregnancy test if you can become pregnant. To continue your
    participation in this study, you cannot be pregnant.

    On Days 0, 7, 14, 22, 28, 35, 43, 49, 56, 64, 70, 77, 84, 112, and 140:

    - You will have a physical exam.

    - Blood (about 5 tablespoons) will be drawn for routine tests, immune system tests, and
    tests on how long the T-cells survive in your body.

    - Between Day 35 and 42 and again between Day 77 and 84, you will have a CT scan to check
    the status of the disease.

    On Day 3, blood (about 5 tablespoons) will be drawn for routine tests, immune system tests,
    and tests on how long the T-cells survive in your body.

    If the doctor thinks it is needed to confirm the status of the disease, blood (about 1
    tablespoons) will be drawn every 3-6 months for up to 3 years.

    The study tests may be repeated or you may have additional tests performed anytime the
    doctor thinks it is needed.

    Some of the study tests may be done at your local clinic if you cannot return to MD
    Anderson. The study staff will discuss this with you.

    Length of Treatment:

    The treatment portion of the study will last until Day 64. You will no longer be able to
    take the study drugs if the disease gets worse, if intolerable side effects occur, or if you
    are unable to follow study directions.

    Your participation on the study will be over after the follow-up.

    End-of-Study Visit:

    At Day 168:

    - You will have a physical exam.

    - Blood (about 5 tablespoons) will be drawn for routine tests, immune system tests, and
    tests on how long the T-cells survive in your body.

    Follow-Up:

    Every 3 months after Day 84, unless the disease gets worse or you start another cancer
    therapy, you will have a CT scan or x-rays to check the status of the disease. Every 3
    months for up to 5 years, the study staff will call you or ask your doctor how you are
    doing. If you are called, the calls should last about 10-15 minutes.

    If the doctor thinks it is needed, you will return to the clinic every 4-6 weeks or as often
    as the doctor thinks is needed. Blood (about 5 tablespoons) will be drawn for routine
    tests, immune system tests, and tests on how long the T-cells survive in your body.

    This is an investigational study. CD8+T cells are not FDA approved or commercially
    available. They are currently being used for research purposes only. Cyclophosphamide,
    ipilimumab, and aldesleukin are FDA approved and commercially available for the way they are
    being used in this study.

    Up to 30 participants will be enrolled in this multicenter study. Up to 20 will take part at
    MD Anderson.

    Trial Arms

    Name Type Description Interventions
    CD8+ T Cells + Cyclophosphamide + Interleukin-2 + Ipilimumab Experimental Leukapheresis procedure performed to collect blood cells so they can be separated and grown as CD8+T cells. Cyclophosphamide administered at 300 mg/m2 by vein 2 days prior to T cell infusion. T cells administered at a dose of 10^10 cells/m2 by vein on Day 0. IL-2 250,000 U/m2 administered subcutaneously every 12 hours begins within 6 hours of T cell infusion and continues for a total of 14 days On Day 0 to Day +14. Ipilimumab administered 24 hours after T cell infusion at a dose of 3 mg/kg by vein. Subsequent infusions administered on Days +22, +43 and +64. Cyclophosphamide, Interleukin-2, Ipilimumab

    Eligibility Criteria

    Inclusion Criteria:

    1. Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic
    disease.

    2. Male or female subjects >/= 18 years of age.

    3. Expression of HLA-A2.

    4. ECOG/ Zubrod performance status of '0-1' at screening visit.

    5. Women of childbearing potential (WOCBP) must be using an adequate method of
    contraception to avoid pregnancy throughout the study in such a manner that the risk
    of pregnancy is minimized. Suggested precautions should be used to minimize the risk
    or pregnancy for at least 1 month before start of therapy, and while women are on
    study for up to 3 months after T cell infusion, and at least 8 weeks after the study
    drug is stopped. WOCBP include any female who has experienced menarche and who has
    not undergone successful surgical sterilization (hysterectomy, bilateral tubal
    ligation or bilateral oophorectomy) or is not postmenopausal.

    6. Men must be willing and able to use an acceptable method of birth control, for at
    least 3 months after completion of the study, if their sexual partners are WOCBP.

    7. Willing and able to give informed consent.

    8. Adequate venous access - consider PICC or central line.

    9. Evaluation of BRAFV600 mutation status.

    10. Measurable tumor (by RECIST criteria).

    11. MART 1 or SLC45A2 (+) staining results. (If patients have not had staining test in
    the past, the test will be run after patient consent is obtained, but before
    enrollment).

    Exclusion Criteria:

    1. Any other malignancy from which the patient has been disease-free for less than 5
    years, with the exception of adequately treated and cured basal or squamous cell skin
    cancer, superficial bladder cancer, carcinoma in situ of the cervix.

    2. Pregnant women, nursing mothers, men or women of reproductive ability who are
    unwilling to use effective contraception. Women of childbearing potential with a
    positive pregnancy test within 3 days prior to entry.

    3. Active and untreated central nervous system (CNS) metastasis (including metastasis
    identified during screening MRI or contrast CT). No signs or symptoms of CNS mets
    within the last 30 days (from enrollment evaluation). No single lesion larger than
    1cm No more than 5 lesions

    4. Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are
    excluded from this study, as are patients with a history of autoimmune disease (e.g.
    Systemic Lupus Erythematosus, vasculitis, infiltrating lung disease) whose possible
    progression during treatment would be considered by the Investigator to be
    unacceptable.

    5. Any underlying medical or psychiatric condition, which in the opinion of the
    Investigator, will make the administration of study drug hazardous or obscure the
    interpretation of adverse events, such as a condition associated with frequent
    diarrhea.

    6. Positive screening tests for HIV, Hep B, and Hep C (referencing blood draw at
    leukapheresis screening). If positive results are not indicative of true active or
    chronic infection, the patient can be treated.

    7. CBC and Chemistry profile prior to cyclophosphamide and T cell infusions: WBC </=
    1000/uL Hct </= 24% or Hemoglobin </=8 g/dL ANC </= 500 Platelets </= 50,000
    Creatinine >/= 3.0 x ULN AST/ALT >/= 2.5 x ULN, Bilirubin >/= 3 x ULN

    8. Steroids are not permitted 3 days prior to T cell infusion and concurrently during
    therapy.

    9. Any non-oncology vaccine therapy used for the prevention of infectious disease within
    1 month before or after any ipilimumab dose.

    10. Patients may not be on any other treatments for their cancer aside from those
    included in the protocol. Patients may not undergo another form of treatment
    concurrently with this study.

    11. Pregnant women, nursing mothers, men or women of reproductive ability who are
    unwilling to use effective contraception. Women of childbearing potential with a
    positive pregnancy test within 3 days prior to entry.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Response

    Secondary Outcome Measures

    Trial Keywords

    Melanoma

    Metastatic

    CD8+ T cells

    White blood cell

    Leukapheresis

    Cyclophosphamide

    Cytoxan

    Neosar

    Interleukin-2

    Aldesleukin

    IL-2

    Proleukin

    Ipilimumab

    Yervoy

    BMS-734016

    MDX010