PHASE II STUDY OF CELLULAR ADOPTIVE IMMUNOTHERAPY USING AUTOLOGOUS CD8+ ANTIGEN-SPECIFIC T CELLS AND ANTI-CTLA4 FOR PATIENTS WITH METASTATIC MELANOMA
CD8+ antigen specific T cells,Cyclophosphamide,Interleukin-2,Ipilimumab
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. Modified 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.
Disease Group: Melanoma
Treatment Agent: CD8+ antigen specific T cells,Cyclophosphamide,Interleukin-2,Ipilimumab
Treatment Location: Only at MDACC
Sponsor: Cancer Prevention Institute of Texas (CPRIT),Stand Up to Cancer funding awarded by the American Association for Cancer Research
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.
IRB Review and Approval Date: 01/22/2015
Recruitment Status: Open
Projected Accrual: A maximum of 30 patients will be enrolled in this study on an intent-to-treat basis, and MDACC will enroll 20 patients. Data from additional 10 patients is available through data sharing on patients enrolled at Fred Hutch.
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).
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 ipilimimab 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.
Information and next steps
Melanoma Medical Oncology
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