Ipilimumab Administered to Stage IIIC Stage IV Melanoma After Reg. T Cell Depletion With Denileukin Diftitox

A Phase II Open-Label Study of Ipilimumab Administered to Stage IIIC and Stage IV Melanoma Patients After Regulatory T Cell Depletion With Denileukin Diftitox

This is an open-label, clinical efficacy study of Ipilimumab in patients with Stage IIIC and Stage IV melanoma who have recently been treated with Denileukin Diftitox. Approximately 42 patients with radiographically measurable melanoma who have received at least one cycle of Denileukin Diftitox will be enrolled and treated in the study.

This is an open-label, clinical efficacy study of Ipilimumab in patients with Stage IIIC and Stage IV melanoma who have recently been treated with Denileukin Diftitox. Approximately 42 patients with radiographically measurable melanoma who have received at least one cycle of Denileukin Diftitox will be enrolled and treated in the study.

Inclusion Criteria:

1. Male or female patients ≥18 years of age;

2. Patients with histological confirmed melanoma (Stage IIIC or Stage IV, American Joint Commission on Cancer);

3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2;

4. Life expectancy ≥3 months;

5. Treatment with Denileukin Diftitox within 42 days prior to first dose of Ipilimumab;

6. At least 1 site of radiographically measurable disease by immune-related response criteria (irRC);

7. Adequate hematologic, renal, and liver function as defined by laboratory values performed within 42 days prior to initiation of dosing:

   • Absolute neutrophil count (ANC) ≥1.0 x 109/L;
   • Platelet count ≥100 x 109/L;
   • Hemoglobin ≥8 g/dL;
   • Serum creatinine ≤3 x upper limit of normal (ULN)
   • Total serum bilirubin ≤2 x ULN;
   • Serum aspartate transaminase (AST/SGOT) or serum alanine transaminase (ALT/SGPT) ≤2x ULN, and ≤3 x ULN if liver metastases are present.

8. Fertile males should use an effective method of contraception during treatment and for at least 3 months after completion of treatment, as directed by their physician;

9. Pre-menopausal females and females <2 years after the onset of menopause should have a negative pregnancy test at Screening. Pre-menopausal females must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of study drug. Females of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year;

10. Before study entry, written informed consent must be obtained from the patient prior to performing any study-related procedures.

Exclusion Criteria:

1. Prior treatment with Ipilimumab;
2. Known hypersensitivity to Ipilimumab or any of its components;
3. Steroids within one week prior to initiation of Ipilimumab.
4. Pre-existing autoimmune colitis.
5. Patients with an allograft requiring immunosuppression;
6. Known positive human immunodeficiency virus (HIV)
7. Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures;
8. Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study.