A Phase III, Multi-Center Controlled Trial With Stratified Randomization Comparing The Efficacy Of Interleukin-2 (IL-2) Plus Histamine Dihydrochloride (HDC) Versus IL-2 Alone To Increase The Duration Of Survival In Patients With AJCC Stage IV Malignant Melanoma With Hepatic Metastasis

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed stage IV melanoma

- Must have radiological evidence of lesions in liver (target or non-target)

- At least 1 measurable lesion outside previously irradiated field

- At least 20 mm by contrast-enhanced CT scan, MRI, medical photography, or
physical exam OR at least 10 mm by spiral CT scan

- No prior or concurrent clinical and/or objective evidence of brain metastasis

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- WHO 0-1

Life expectancy:

- At least 3 months

Hematopoietic:

- Hemoglobin at least 9.5 g/dL

- WBC at least 3,000/mm^3

- Granulocyte count at least 2,000/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin no greater than 2 times upper limit of normal (ULN)

- AST and ALT no greater than 4 times ULN

- Alkaline phosphatase no greater than 4 times ULN

- Hepatitis B and C negative

Renal:

- Creatinine no greater than 1.7 mg/dL

- Calcium no greater than 11.5 mg/dL

Cardiovascular:

- No abnormal thallium stress test

- No acute myocardial infarction within the past year

- No New York Heart Association class III or IV heart disease

Pulmonary:

- No asthma requiring active treatment within the past 5 years

- Oxygen saturation by pulse oximeter at least 90% unless FEV_1 is greater than 2 L or
at least 75% predicted

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- Concurrent medically-controlled (except with glyburide) or diet-controlled diabetes
is allowed

- Concurrent medically-controlled thyroid dysfunction is allowed

- No other active malignancy within the past 5 years except carcinoma in situ of the
cervix or localized squamous cell or basal cell skin cancer

- No serious non-malignant medical conditions, including psychiatric disability, that
would preclude study compliance

- No active autoimmune disease (e.g., lupus, inflammatory bowel disease, or psoriasis)

- No active peptic and/or esophageal ulcer disease

- No hypersensitivity to histamine products or urticaria

- No active IV drug abuse

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior immunotherapy with high-dose IV interleukin-2 (IL-2)

- No prior combination immunotherapy with chemotherapy

- At least 1 year since prior low-dose adjuvant IL-2 as part of vaccine therapy or as
therapy for stage II or III melanoma

Chemotherapy:

- See Biologic therapy

Endocrine therapy:

- No chronic systemic glucocorticoid steroids

- Asthma inhalers, topical creams, or intra-articular injections allowed

- Hormonal therapy for non-melanoma-related conditions allowed

Radiotherapy:

- See Disease Characteristics

- Concurrent radiotherapy as palliative therapy for isolated non-target lesions (e.g.,
bone lesions) allowed

Surgery:

- Not specified

Other:

- At least 4 weeks since prior therapy directed at malignancy

- At least 4 weeks since prior investigational medications or therapies

- At least 2 weeks since prior parenteral antioxidants and/or vitamins

- At least 2 weeks since prior antibiotics for active illness

- At least 2 weeks since prior H2 antagonists, beta-blockers, antihypertensives,
antimalarials, antitrypanosomals, neuromuscular-blocking agents, tricyclic
antidepressants, or alprazolam

- At least 24 hours since prior antihistamines

- No prior enrollment in any Maxim Pharmaceuticals investigational trials

- No concurrent anticonvulsant therapy for seizure disorder

- No other concurrent investigational drug

- No concurrent H2 antagonists, tricyclic antidepressants, alprazolam, beta- blockers,
antihypertensives, antitrypanosomals, antimalarials, or monoamine oxidase inhibitors

- No concurrent inhibitors of diamine oxidase, monoamine oxidase, or histamine
N-methyltransferase

- No concurrent antihistamines