Phase II Trial of Ipilimumab in Patients With Advanced Melanoma and Spontaneous Preexisting Immune Response to NY-ESO-1
- Histologic diagnosis of malignant melanoma; unresectable Stage III melanoma or Stage
IV melanoma; Measurable/evaluable disease (as per mWHO criteria), within 28 days
before first dose of study drug;
- Preexisting spontaneous immune response to NY-ESO-1, defined by positive results in
ELISA above a prespecified cut-off value.
- Previously treated or untreated metastatic melanoma. The previous treatment must have
been finished at least 28 days before the first ipilimumab administration. Patients
must have recovered from any acute toxicity associated with prior therapy
- Life expectancy of ≥ 16 weeks;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- Men and women, ages 18 and above.
- Ability of subject to understand character and individual consequences of the
- Required values for initial laboratory tests:
- WBC ≥ 2000/μL
- ANC ≥ 1000/μL
- Platelets ≥ 100 x 103/μL
- Hemoglobin ≥ 9 g/dL (may be transfused)
- Creatinine ≤ 2 x ULN
- AST/ALT ≤ 2.5 x ULN for subjects without liver metastasis≤ 5 x ULN for subjects
with liver metastasis
- Bilirubin ≤ 2.0 x ULN
- Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study
- Brain Metastasis, unless previously treated, off steroids for at least 4 weeks and
considered to be stable (eg, no progression of the treated lesion);
- Primary ocular or mucosal melanoma
- Prior malignancy active within the previous 5 years except for locally curable
cancers that have been adequately treated, such as basal or squamous cell skin
- Autoimmune disease: subjects with a documented history of inflammatory bowel disease,
including ulcerative colitis and Crohn's disease are excluded from this study as are
subjects with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune
vasculitis [e.g., Wegener's Granulomatosis]). Subjects with motor neuropathy
considered of autoimmune origin (e.g., Guillain-Barre Syndrome) are excluded from
- 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 AEs, such as a condition associated with frequent diarrhea.
- Previous participation with a NY-ESO 1 derived vaccination study.
- Inadequate hematologic function defined by an absolute neutrophil count (ANC) <
1,000/mm3, a platelet count < 100,000/mm3, or a hemoglobin level < 9 g/dL;
- Inadequate hepatic function defined by a total bilirubin level > 2.0 x ULN except
subjects with Gilbert's Syndrome, who must have a total bilirubin < 3.0 ULN. AST and
ALT levels ≥ 2.5 times the ULN, or ≥ 5 times the ULN if liver metastases are present;
- Inadequate renal function defined by a serum creatinine level ≥ 2.0 times the ULN, or
inadequate creatinine clearance defined as less than 50 mL/min;
- Positive tests for HIV, Hepatitis B, and Hepatitis C. If positive results are not
indicative of true active or chronic infection, the patient can enter the study after
discussion and agreement with the investigator and the Medical Monitor.
- Chronic use of immunosuppressants and/or systemic corticosteroids (used in the
management of cancer or non-cancer-related illnesses).
- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up
to 4 weeks prior to or after any dose of ipilimumab);
- Prior treatment with a CD137 agonist, ipilimumab or other CTLA-4 inhibitor.
- Prisoners or subjects who are involuntarily incarcerated
- Participation in other clinical trials or observation period of competing trials,
respectively during the last 30 days before the first application of the
investigational agent .