Ipilimumab and Local Radiation for Selected Solid Tumors

Inclusion Criteria

• •Willing and able to give written informed consent
• •* Before any study procedures are performed, subjects (or their legally acceptable representatives) will have the details of the study described to them, and they will be given a written informed consent document to read; then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel
• •Histologically confirmed malignancy
• •* In Phase 1, histologically confirmed melanoma.
• •* In Phase 2, histologically confirmed melanoma, non-Hodgkin lymphoma, or colorectal carcinoma
• •Must have failed at least 1 systemic therapy or be intolerant to at least one prior systemic treatment
• •Must have at least 2 lesions of evaluable size by modified World Health Organization (mWHO)/Cheson criteria; 1 of 2 lesions must be amenable to biopsy (core or fine needle aspirate) and intratumoral injection of up to 5 mL (diameter ≥ 10mm)
• •Subjects with asymptomatic brain metastases are eligible; (systemic steroids should be avoided if possible, or the subject should be stable on the lowest clinically effective dose, as steroids as they may interfere with the activity of ipilimumab if administered at the time of the first ipilimumab dose)
• •Must be at least 28 days since treatment with standard or investigational chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• •Life expectancy of ≥ 16 weeks
• •Subjects must have baseline (screening/baseline) radiographic images, (e.g. brain, chest, abdomen, pelvis, and bone scans with specific imaging tests to be determined by the attending physician) within 6 weeks of initiation of ipilimumab
• •White blood cell (WBC) ≥ 2000/uL (\~2 x 10\^9/L)
• •Absolute neutrophil count (ANC) ≥ 1000/uL (\~0.5 x 10\^9/L)
• •Platelets ≥ 75 x 10\^3/uL (\~75 x 10\^9/L)
• •Hemoglobin ≥ 9 g/dL (may be transfused)
• •Creatinine ≤ 2.0 x upper limit of normal (ULN)
• •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN for subjects without liver metastasis ≤ 5 times for liver metastases
• •Bilirubin ≤ 2.0 x ULN (except for subjects with Gilbert's syndrome, who must have a total bilirubin of less than 3.0 mg/dL)
• •No active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• •Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized; 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 post-menopausal; post-menopause is defined as:
• •* Amenorrhea ≥ 12 consecutive months without another cause, or
• •* For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level ≥ 35 mIU/mL
• •Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 72 hours before the start of ipilimumab
• •Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study (and for up to 26 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized