Clinical Trials /

Adoptive Therapy Using Antigen-Specific CD4 T-Cells

NCT02210104

Description:

The goal of this clinical research study is to learn about the safety of giving CD4+T cells with ipilimumab and cyclophosphamide. CD4+T cells are a type of white blood cell. Researchers grow the T cells in the laboratory, and they are designed to find cancer cells and may kill them.

Related Conditions:
  • Liposarcoma
  • Melanoma
  • Synovial Sarcoma
Recruiting Status:

Withdrawn

Phase:

Phase 1

Trial Eligibility

Document

Adoptive Therapy Using Antigen-Specific CD4 T-Cells

Title

  • Brief Title: Adoptive Therapy Using Antigen-Specific CD4 T-Cells
  • Official Title: Phase I Study of Cellular Adoptive Immunotherapy Using Autologous CD4+ NY-ESO-1-Specific T Cells and Anti-CTLA4 For Patients With NY-ESO-1-Expressing Tumors
  • Clinical Trial IDs

    NCT ID: NCT02210104

    ORG ID: 2013-0669

    NCI ID: R01CA104711-09

    Trial Conditions

    Melanoma

    Sarcoma

    Trial Interventions

    Drug Synonyms Arms
    Ipilimumab Yervoy, BMS-734016, MDX010 Ipilimumab + Cyclophosphamide + CD4+T Cells
    Cyclophosphamide Cytoxan, Neosar Ipilimumab + Cyclophosphamide + CD4+T Cells

    Trial Purpose

    The goal of this clinical research study is to learn about the safety of giving CD4+T cells
    with ipilimumab and cyclophosphamide.

    CD4+T cells are a type of white blood cell. Researchers grow the T cells in the laboratory,
    and they are designed to find cancer cells and may kill them.

    Detailed Description

    Study Groups:

    If you are found to be eligible to take part in this study, you will be assigned to a study
    group based on when you join this study. The first 3 or 6 participants will receive a lower
    dose of ipilimumab. If there are no intolerable side effects, then the second group of 6
    participants will receive a higher dose of ipilimumab.

    All study participants will receive the same dose level of cyclophosphamide and the CD4+T
    cells.

    Study Drug Administration:

    You will receive cyclophosphamide by vein over about 30-60 minutes on Day -2 (2 days before
    you receive the CD4+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 drugs are given and their risks.

    On Day 0, you will receive the CD4+T cells by vein over about 30-60 minutes. You will stay
    in the hospital overnight after the dose.

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

    Study Visits:

    Within 2-4 weeks before you receive the CD4+T cells:

    - 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.

    - You will have a computed tomography (CT) scan or x-rays to check the status of the
    disease.

    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.

    On Day 1:

    - You will have a physical exam.

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

    On Days 0, 7, 14, 22, 28, 35, 43, 49, and 56:

    - 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.

    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.

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

    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 Study Drug Dosing:

    Your last study drug dose will be on 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-Drug-Dosing Visit:

    On Day 64:

    - 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:

    On Days 70, 77, 84, 105, 126, 147, and 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.

    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 to confirm the status of the disease, blood (about 1
    tablespoons) will be drawn every 3 months for up to 1 year.

    If the doctor thinks it is needed, you will return to the clinic every 4-6 weeks starting
    after Day 168 or as often as the doctor thinks is needed. These visits will stop if the
    T-cells disappear or if the disease gets worse. 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. CD4+T cells are not FDA approved or commercially
    available. They are currently being used for research purposes only. Cyclophosphamide is FDA
    approved and commercially available for the way it is being used in this study. Ipilimumab
    is FDA approved and commercially available for the treatment of melanoma, but not for
    sarcoma. The study doctor can explain how the study drugs are designed to work.

    Up to 12 participants will be enrolled in this study. All will take part at MD Anderson.

    Trial Arms

    Name Type Description Interventions
    Ipilimumab + Cyclophosphamide + CD4+T Cells Experimental Starting Dose of Ipilimumab 1.0 mg /kg by vein on Days 1, 22, 43, and 64. Cyclophosphamide 300 mg/m2 administered intravenously 2 days prior to T cell infusion as an outpatient procedure. Antigen-specific CD4+ T cells administered at a dose 10^10 cells/m^2. Ipilimumab, Cyclophosphamide

    Eligibility Criteria

    Inclusion Criteria:

    1. Histopathologic documentation of melanoma, synovial sarcoma or mixed round cell
    liposarcoma concurrent with the diagnosis of metastatic disease.

    2. Tumor expression of NY-ESO-1 (2+ staining or > 25%) by IHC.

    3. Male or female subjects 18 years of age.

    4. Expression of HLA-DPB1*0401

    5. Eastern Cooperative Oncology Group (ECOG)/ Zubrod performance status of '0-1' .

    6. 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

    7. 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.

    8. Willing and able to give informed consent.

    9. Adequate venous access - consider peripherally inserted central venous catheter
    (PICC) or central line

    10. Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic
    imaging (X-ray or CT scan)

    11. At least 4 weeks must have elapsed since the last chemotherapy, immunotherapy,
    radiotherapy, or major surgery.

    12. At least 6 weeks must have elapsed since the last nitrosoureas, mitomycin C and
    liposomal doxorubicin

    13. Toxicity related to prior therapy must either have returned to < or equal to grade 1,
    baseline, or been deemed irreversible

    Exclusion Criteria:

    1. Patients with active infections or oral temperature > 38.2 C within 71 hours of
    Leukapheresis. The procedure may be deferred.

    2. Patients with Hct <30%, white blood count (WBC) <2500/uL and platelets <50,000
    immediately prior to Leukapheresis. The procedure may be deferred.

    3. 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.

    4. Complete blood count (CBC) and Chemistry profile prior to cyclophosphamide and T cell
    infusions: WBC < 2000/uL Hct < 24% or Hb < 8 g/dL absolute neutrophil count (ANC) <
    1000 Platelets < 50,000 Creatinine > 3.0 x ULN AST/ALT > 2.5 x ULN Bilirubin > 3 x
    ULN

    5. 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.

    6. Clinically significant pulmonary dysfunction, as determined by medical history and
    physical exam. Patients so identified will undergo pulmonary functions testing and
    those with FEV1 < 2.0 L or DLco (corr for Hgb) < 75% will be excluded.

    7. Significant cardiovascular abnormalities as defined by any one of the following:
    Congestive heart failure, Clinically significant hypotension, Symptoms of coronary
    artery disease, Presence of cardiac arrhythmias on EKG requiring drug
    therapy,Ejection fraction < 50 % (echocardiogram or MUGA).

    8. Active and untreated central nervous system (CNS) metastasis (including metastasis
    identified during screening MRI or contrast CT).

    9. 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.

    10. 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.

    11. Positive screening tests for HIV, Hep B, and Hep C. If positive results are not
    indicative of true active or chronic infection, the patient can be treated.

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

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

    14. No prisoners or children will be enrolled on this study

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose (MTD) of Adoptively Transferred CD4 T Cells

    Secondary Outcome Measures

    Clinical Response

    Trial Keywords

    Melanoma

    Sarcoma

    Mixed round cell liposarcoma

    Advanced

    Metastatic

    Immunotherapy

    Ipilimumab

    Yervoy

    BMS-734016

    MDX010

    Cyclophosphamide

    Cytoxan

    Neosar

    CD4+T Cells