PI departure, operational issues

The purpose of this research study is to see if the combination of HSPPC-96 and ipilimumab is safe and effective in the treatment of advanced melanoma. HSPPC-96 is an investigational vaccine created from tissue from the patient's tumor. The vaccine is designed to capture the cancer's "fingerprint." Injection of the vaccine may cause the patient's immune system to recognize and attack any cells with the specific cancer fingerprint. Ipilimumab is a drug approved by the FDA for the treatment of metastatic melanoma that boosts immune response.

This is a randomized, open label, single-center, phase I-II trial to determine the safety, feasibility and immunogenicity of combination treatment of HSPPC-96 and ipilimumab in patients with therapeutically unresectable Stage III or Stage IV malignant melanoma.

The main purpose of this study is to assess whether the administration of the combination of ipilimumab and HSPPC-96 is safe. The rationale for combining the two treatments resides in their respective roles on the immune system as described below and based on the clinical experience collected so far. HSPPC-96 is able to initiate a tumor specific immune response that ipilimumab could theoretically amplify by blocking a checkpoint that naturally down-regulates T cells.

Inclusion Criteria:Pre-surgery Inclusion criteria:

• Signed informed consent

• ≥ 18 years of age

• Stage III or Stage IV melanoma according to TNM staging criteria/AJCC version 7 determined by PET/MRI/CT scan

• ECOG score 0 or 1

• Life expectancy ≥6 months

• Candidate for surgical resection with viable melanoma tissue to ascertain ≥ 7 grams of viable cancer tissue (in aggregate), which is equivalent to a ≥ 2 cm lesion on CT/MRI or clinical examination

• Adequate cardiac function (≤ NYHA class II)

• Adequate bone marrow function, including: absolute granulocyte count (ANC) ≥ 1,500x106/L, absolute lymphocyte count (ALC) ≥ 500/mm3, platelets count ≥100,000 x 106/mm3. Adequate liver function including: serum glutamic oxaloacetic transaminases/aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the upper limit of institutional normal (IULNs), bilirubin ≤ 1.5 mg/dL or 25 µmol/L (SI units). Adequate renal function: BUN and Serum creatinine of ≤ 1.5 mg/dL or 130 µmol/L (SI units)

• Female subjects of childbearing potential and fertile males must agree to use adequate contraception during the course of the study. Adequate contraception includes condoms with contraceptive foam; oral, implantable or injectable contraceptives; contraceptive patch; intrauterine device; diaphragm with spermicidal gel; or a sexual partner who is surgically sterilized or postmenopausal.

  • Post-surgery Inclusion Criteria (must be completed within 4 weeks of surgery)

• Histologically and clinically confirmed Stage III and/or Stage IV malignant melanoma according to TNM Staging Criteria/AJCC version 7 confirmed by PET/CT scan

• Measurable disease for target lesion clinical and radiological monitoring

• ECOG score 0 or 1

• Adequate cardiac function (≤ NYHA class II)

• Adequate bone marrow function, liver, and renal function

• ≥ 6 doses of vaccine for clinical use

Exclusion Criteria: Pre-Surgery Exclusion Criteria:

• Primary mucosal or primary ocular melanomas

• Other malignancies treated within the last five years, except in situ cervix carcinoma or non-melanoma skin cancer

• Primary or secondary immunodeficiency (including immunosuppressive disease, or systemic use of corticosteroids or other immunosuppressive medications)

• Patients with history of HIV1 and 2, HTLV-1, HBV or active HCV.

• Patients with history of connective tissue disorders

• Prior ipilimumab or melanoma vaccine therapy

• Prior therapy with IL-2

• Prior chemotherapy, small molecule targeted therapy, interferon within 3 months prior to enrollment

• Prior investigational products administration within 4 weeks prior to enrollment

• Prior splenectomy

• Symptomatic CNS metastases or spinal cord compression

• Uncontrolled infection or other serious medical illnesses

• Any medical conditions that, in the opinion of the investigator, would preclude use of ipilimumab, including ipilimumab hypersensitivity

• Women who are pregnant or breast-feeding

• Concurrent participation in investigational trials

  • Post-surgery Exclusion Criteria (must be completed within 4 weeks of surgery):

• Emergence of contraindicated clinical condition