PHASE Ib STUDY OF CELLULAR ADOPTIVE IMMUNOTHERAPY USING AUTOLOGOUS CD8+ ANTIGEN-SPECIFIC T CELLS AND ANTI-CTLA4 FOR PATIENTS WITH METASTATIC UVEAL MELANOMA
CD8+ antigen specific T cells,Cytoxan,Interleukin-2,Ipilimumab
Sapna P. Patel
This clinical research study is divided into 2 parts: leukapheresis and treatment. In the leukapheresis part, white blood cells called T cells will be collected from you to be made into specialized CD8+T cells. To make specialized CD8+T cells, researchers separate out T cells from blood and treat them so they are able to target melanoma cells. The blood cells are then given back to the patient in the treatment part of the study. This is known as "adoptive T cell transfer" or "adoptive T cell therapy". This consent form is for the treatment part of the study. The goal of this clinical research study is to learn about the safety of giving CD8+T cells with cyclophosphamide, and IL-2 (aldesleukin) to patients with uveal melanoma that is metastatic (has spread). Some participants will also receive ipilimumab. Researchers also want to learn if this combination can help to control the disease.
Disease Group: Melanoma and other malignant neoplasms of skin,Symptoms and signs involving the skin and subcutaneous tissue
Treatment Agent: CD8+ antigen specific T cells,Cytoxan,Interleukin-2,Ipilimumab
Treatment Location: Only at MDACC
Primary Objectives: To determine the maximum tolerated dose (MTD) of adoptively transferred SLC45A2-specific CTL for the treatment of patients with metastatic uveal melanoma. Secondary Objectives: To establish the anti-tumor efficacy as measured by immune-related response criteria (irRC) and duration of response in metastatic uveal melanoma patients receiving autologous CD8+ T cells against SLC45A2. To assess the safety and tolerability of adoptively transferred SLC45A2-specific CTL in combination with immune checkpoint blockade in metastatic uveal melanoma patients. To quantify in vivo numeric and functional persistence of transferred CTL, and development of antigen spreading. To assess overall survival and progression-free survival in metastatic uveal melanoma patients.
IRB Review and Approval Date: 09/08/2017
Recruitment Status: Open
Projected Accrual: N/A
1) Eligibility for Pheresis: (Turnstile 1) Histopathologic documentation
of melanoma concurrent with the diagnosis of metastatic disease. A
diagnosis of uveal melanoma can be made clinically without primary
tissue evaluation, based on history and records. A prior history of
brachytherapy to the eye is sufficient clinical support for a diagnosis
of uveal melanoma.
2) Male or female subjects >/= 18 years of age.
3) Expression of HLA-A:0201 or HLA-A:2402.
4) ECOG/ Zubrod performance status of 0-1.
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 completion of the study. 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) Male patients must be willing and able to use an acceptable method of birth control, during and 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) Toxicity related to prior therapy must either have returned to </= grade 1, baseline, or been deemed irreversible. Certain non-serious exceptions include alopecia, hypothyroidism, neuropathy, nausea, adrenocortical deficiency requiring physiologic replacement dose of steroids, and other conditions noted and approved by the PI.
9) Eligibility for T cell infusion (Includes Cyclophosphamide, T cell, anti-CTLA4 infusions and s.c. IL-2) (Turnstile 2) (Note: evaluate at least 1 week before T cell infusion). ECOG/Zubrod performance status of 0-1.
10) Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging per irRC.
11) At least 4 weeks must have elapsed since the last chemotherapy, targeted therapy, immunotherapy, radiotherapy, liver-directed therapy, or major surgery. At least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin. If started before T-cell administration, ipilimumab infusions must be least 21 days apart.
12) Toxicity related to prior therapy must either have returned to </=grade 1, baseline, or been deemed irreversible. Certain non-serious exceptions include alopecia, hypothyroidism, neuropathy, nausea, adrenocortical deficiency requiring physiologic replacement dose of steroids, and other conditions noted and approved by the PI.
13) Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 3 months after completion of study.
14) Willing and able to give informed consent.
15) Patients must have liver metastases.
1) Exclusion Criteria for Leukapheresis: Any other malignancy from which
the patient has been disease-free for less than 2 years, with the
exception of adequately treated and cured basal or squamous cell skin
cancer, superficial bladder cancer, carcinoma in situ of the cervix or
breast, or melanoma in-situ.
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 pheresis.
3) 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) < 50% will be excluded.
4) Significant cardiovascular abnormalities as defined by any one of the following: • Congestive heart failure, • Clinically significant hypotension, • Symptoms of coronary artery disease (angina, dyspnea), • Presence of cardiac arrhythmias on EKG requiring drug therapy,
5) 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. Acceptable exclusions include: Hashimoto’s thyroiditis, Type 1 diabetes mellitus, and other localized or inactive conditions with approval of the PI.
6) 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.
7) 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.
8) Exclusion Criteria for Treatment: a CBC and Chemistry profile prior to cyclophosphamide and T cell infusions: • WBC </= 2000/uL • Hct </= 24% or Hb </=8 g/dL • ANC </= 1000 • Platelets </= 50,000 • Creatinine >/= 3.0 x ULN • AST/ALT </= 5 x ULN (since all patients will have liver metastasis) • Bilirubin >/=3 x ULN
9) 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.
10) Steroids (at prednisone equivalent doses > 10 mg) are not permitted 3 days prior to T cell infusion and concurrently during therapy. Exceptions include use of systemic prednisone equivalent doses </= 10 mg/ day, topical steroids or physiologic replacement dose of steroids for adrenocortical deficiency.
11) Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose.
12) 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. Oncology supportive treatments such as growth factors, bone modifying agents, pain or nausea management are allowed.
13) Participation in any other immunotherapy treatment, that in the opinion of the principal investigator would be unsafe to receive further checkpoint blockade immunotherapy.
Information and next steps
Melanoma and other malignant neoplasms of skin,Symptoms and signs involving the skin and subcutaneous tissue
Sapna P. Patel
Melanoma Medical Oncology
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