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Interleukin-2 With or Without Histamine Dihydrochloride in Treating Patients With Stage IV Melanoma Metastatic to the Liver

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00039234
Recruitment Status : Unknown
Verified December 2003 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : January 27, 2003
Last Update Posted : December 18, 2013
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Histamine dihydrochloride may help interleukin-2 kill more tumor cells by making tumor cells more sensitive to the drug. It is not yet known if interleukin-2 is more effective with or without histamine dihydrochloride in treating stage IV melanoma that is metastatic to the liver.

PURPOSE: Randomized phase III trial to compare the effectiveness of interleukin-2 with or without histamine dihydrochloride in treating patients who have stage IV melanoma that is metastatic to the liver.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Metastatic Cancer Biological: aldesleukin Drug: histamine dihydrochloride Phase 3

Detailed Description:


  • Compare the duration of survival in patients with stage IV melanoma with hepatic metastasis treated with interleukin-2 with or without histamine dihydrochloride.
  • Compare the progression-free survival, response rate, response rate of hepatic tumors, and lack of disease progression in patients treated with these regimens.
  • Determine the safety of these regimens, in terms of frequency, severity, and causal relationship of adverse events, in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center location (North America vs Europe), lactate dehydrogenase (less than ULN vs ULN or greater), and metastatic sites (liver only vs liver and other sites). Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive interleukin-2 (IL-2) subcutaneously (SC) twice daily on days 1 and 2 of weeks 1 and 3 and days 1-5 of weeks 2 and 4. Patients also receive histamine dihydrochloride SC over 10-30 minutes on days 1-5 of weeks 1-4.
  • Arm II: Patients receive IL-2 as in arm I. In both arms, treatment repeats every 6 weeks for at least 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 3 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 224 patients (112 per treatment arm) will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2002

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status:

  • WHO 0-1

Life expectancy:

  • At least 3 months


  • 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


  • 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


  • Creatinine no greater than 1.7 mg/dL
  • Calcium no greater than 11.5 mg/dL


  • No abnormal thallium stress test
  • No acute myocardial infarction within the past year
  • No New York Heart Association class III or IV heart disease


  • 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


  • 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


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


  • 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


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


  • Not specified


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00039234

Show Show 19 study locations
Sponsors and Collaborators
Maxim Pharmaceuticals
National Cancer Institute (NCI)
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Study Chair: John A. Glaspy, MD, MPH Jonsson Comprehensive Cancer Center
Layout table for additonal information Identifier: NCT00039234    
Other Study ID Numbers: CDR0000069365
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: December 18, 2013
Last Verified: December 2003
Keywords provided by National Cancer Institute (NCI):
stage IV melanoma
recurrent melanoma
liver metastases
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Histamine phosphate
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Histamine Agonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs