This phase II trial studies how well high-dose aldesleukin and ipilimumab works in treating
patients with stage III-IV melanoma that cannot be removed by surgery. Biological therapies,
such as aldesleukin, may stimulate or suppress the immune system in different ways and stop
tumor cells from growing. Monoclonal antibodies, such as ipilimumab, interfere with the
ability of tumor cells to grow and spread. Giving high-dose aldesleukin together with
ipilimumab may work better in treating patients with melanoma.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- Willing and able to give written informed consent
- Histologic or cytologic diagnosis of cutaneous melanoma that is considered
unresectable (stage III) or metastatic (stage IV); ocular and mucosal melanoma is
excluded
- White blood cell (WBC) >= 2000/uL
- Absolute neutrophil count (ANC) >= 1000/uL
- Platelets >= 75 x 10^3/uL
- Hemoglobin >= 9 g/dL (>= 80 g/L; may be transfused)
- Creatinine =< 2. 0 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2. 5 x ULN for
patients without liver metastasis, =< 5 times for patients with liver metastases
- Bilirubin =< 2. 0 x ULN, (except patients with Gilbert's syndrome, who must have a
total bilirubin less than 3. 0 mg/dL)
- No known active or chronic infection with human immunodeficiency virus (HIV),
hepatitis B, or hepatitis C; testing is not required unless clinically suspected
- Performance status (Eastern Cooperative Oncology Group [ECOG] 0-1)
- Patients must have a life expectancy of greater than three months at the start of the
trial
- Patients must have a brain magnetic resonance imaging (MRI) that is free of active
metastases; metastases that have been treated with radiation or surgical resection,
are stable for at least 4 weeks and do not require steroids are eligible
- Patients may have received treatment of completely resected early stage melanoma,
comprising interferon, radiation treatment, or experimental vaccine therapy, and in
the metastatic setting patient can have had treatment such as chemotherapy,
immunotherapy (except prior treatment with ipilimumab and IL-2), and other
experimental agent which was completed 4 weeks prior to enrollment
- Normal cardiac stress test for patients over 50 years of age
- Forced expiratory volume in 1 second (FEV1) > 65% of prediction for those patients
with extensive pulmonary metastases or chronic pulmonary disease history
- Forced vital capacity (FVC) > 65% of prediction for those patients with extensive
pulmonary metastases or chronic pulmonary disease history
- 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; in general, the decision for appropriate methods to prevent pregnancy
should be determined by discussions between the investigator and the study subject;
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
Exclusion Criteria:
- Any other malignancy form 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 or carcinoma in situ of the cervix
- Patients with primary ocular or mucosal melanoma are excluded
- Patients with a history of inflammatory bowel disease, including ulcerative colitis
and Crohn's disease, are excluded from this study, as are patients with a history of
symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis
[scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's
granulomatosis]); motor neuropathy considered of autoimmune origin (e. g.
Guillain-Barre syndrome and Myasthenia Gravis)
- Any underlying medical or psychiatric condition, which in the opinion of the
investigator will make the administration of ipilimumab hazardous or obscure the
interpretation of adverse events (AEs), such as a condition associated with frequent
diarrhea
- Patients with underlying heart conditions who are deemed ineligible for surgery by
cardiology consult; patients with reversible ischemic changes on cardiac stress test
- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up
to 1 month before or after any dose of ipilimumab)
- A history of prior treatment with IL-2, ipilimumab or prior cytotoxic T-lymphocyte
antigen 4 (CTLA4) inhibitor or agonist
- Concomitant therapy with any of the following: interferon, or other non-study
immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other
investigation therapies; or chronic use of systemic corticosteroids
- Women of childbearing potential (WOCBP), who:
- Are unwilling or unable to use an acceptable method of contraception to avoid
pregnancy for their entire study period and for at least 8 weeks after cessation
of study drug, or
- Have a positive pregnancy test at baseline, or
- Are pregnant or breastfeeding
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (eg, infectious) illness
Loyola University Medical Center, Maywood, Illinois 60153, United States; Not yet recruiting
Joseph I. Clark, Phone: 708-226-4357
Joseph I. Clark, Principal Investigator
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States; Not yet recruiting
David F. McDermott, Phone: 617-667-9925
David F. McDermott, Principal Investigator
Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States; Not yet recruiting
Marc S. Ernstoff, Phone: 603-650-7609, Email: cancerhelp@dartmouth.edu
Marc S. Ernstoff, Principal Investigator
Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, United States; Recruiting
Clinical Trials Office, Phone: 732-235-8675
Howard L. Kaufman, Principal Investigator
Providence Portland Medical Center, Portland, Oregon 97213, United States; Recruiting
Brendan D. Curti, Phone: 503-215-6412
Brendan D. Curti, Principal Investigator
Vanderbilt University Medical Center, Nashville, Tennessee 37240, United States; Not yet recruiting
Jeffrey A. Sosman, Phone: 800-811-8480
Jeffrey A. Sosman, Principal Investigator