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Monoclonal Antibody Therapy and Interleukin-2 in Treating Patients With Metastatic Melanoma

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.
 
ClinicalTrials.gov Identifier: NCT00058279
Recruitment Status : Completed
First Posted : April 9, 2003
Last Update Posted : June 20, 2013
Sponsor:
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Biological therapies, such as MDX-010, work in different ways to stimulate the immune system and stop tumor cells from growing. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining monoclonal antibody therapy with interleukin-2 may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining monoclonal antibody therapy with interleukin-2 in treating patients who have metastatic melanoma.


Condition or disease Intervention/treatment Phase
Intraocular Melanoma Melanoma (Skin) Biological: aldesleukin Biological: ipilimumab Phase 1 Phase 2

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose (MTD) of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4) in combination with high-dose interleukin-2 (IL-2) in patients with metastatic melanoma. (Phase I is closed to accrual as of 4/13/2004).
  • Determine the activity of MDX-CTLA4 administered at the MTD with high-dose IL-2 in these patients.
  • Determine whether the administration of IL-2 alters the pharmacokinetics of MDX-CTLA4 in these patients.
  • Determine the safety and adverse event profile of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4).

  • Phase I: Patients receive MDX-CTLA4 IV on days 0, 21, and 42. Patients also receive high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours for up to 15 doses beginning on days 22 and 43. Treatment repeats every 63 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with an ongoing partial response and no greater than grade 1 toxicity may receive additional courses of therapy. Patients who require discontinuation of MDX-CTLA4 due to toxicity may continue receiving IL-2 at the discretion of the investigator.

Cohorts of 3-6 patients receive escalating doses of MDX-CTLA4 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. (Phase I is closed to accrual as of 4/13/2004).

  • Phase II: Patients receive treatment as in phase I at the MTD of MDX-CTLA4. Patients who achieve a partial or complete response and later develop recurrent or progressive disease may be retreated at the same dose.

Patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-51 patients (3-18 for phase I and 19-33 for phase II) will be accrued for this study within 1 year. (Phase I is closed to accrual as of 4/13/2004).

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Study Type : Interventional  (Clinical Trial)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MDX-CTLA4 Combined With IL-2 for Patients With Metastatic Melanoma
Study Start Date : February 2003
Actual Study Completion Date : August 2006






Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed stage IV melanoma

    • Mucosal or ocular melanoma also eligible
  • Clinically evaluable disease

    • At least 1 site of measurable disease

PATIENT CHARACTERISTICS:

Age

  • 16 and over

Performance status

  • ECOG 0-1

Life expectancy

  • At least 3 months

Hematopoietic

  • WBC at least 2,500/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10 g/dL
  • Hematocrit at least 30%

Hepatic

  • Bilirubin no greater than upper limit of normal (ULN)* (less than 3.0 mg/dL in patients with Gilbert's syndrome)
  • AST no greater than 3 times ULN*
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody nonreactive
  • No evidence or history of significant hepatic disease that would preclude safe administration of high-dose IL-2 NOTE: *Unless attributable to disease

Renal

  • Creatinine no greater than 2.0 mg/dL
  • No evidence or history of significant renal disease that would preclude safe administration of high-dose IL-2

Cardiovascular

  • No evidence or history of significant cardiac disease that would preclude safe administration of high-dose IL-2
  • Thallium stress test normal (for patients over 50 years of age or with a history of cardiovascular disease)

Pulmonary

  • No evidence or history of significant pulmonary disease that would preclude safe administration of high-dose IL-2

Immunologic

  • HIV negative
  • No autoimmune disease (including uveitis and autoimmune inflammatory eye disease)
  • No active infection

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
  • No evidence or history of significant gastrointestinal disease that would preclude safe administration of high-dose IL-2
  • No evidence or history of psychiatric disease that would preclude safe administration of high-dose IL-2
  • No other underlying medical condition that would make the administration of the study drug hazardous or obscure the interpretation of adverse events
  • No other concurrent medical condition that would preclude study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 3 weeks since prior immunotherapy for melanoma and recovered
  • No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4)
  • No prior high-dose (at least 600,000 IU/kg every 8 hours) interleukin-2 (IL-2)

Chemotherapy

  • At least 3 weeks since prior chemotherapy for melanoma and recovered
  • No concurrent chemotherapy

Endocrine therapy

  • At least 3 weeks since prior hormonal therapy for melanoma and recovered
  • At least 4 weeks since prior corticosteroids
  • No concurrent systemic or topical corticosteroids

Radiotherapy

  • At least 3 weeks since prior radiotherapy for melanoma and recovered

Surgery

  • Not specified

Other

  • No concurrent immunosuppressive agents (e.g., cyclosporine or its analog)

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 ClinicalTrials.gov identifier (NCT number): NCT00058279


Locations
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United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Study Chair: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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ClinicalTrials.gov Identifier: NCT00058279    
Obsolete Identifiers: NCT00055211
Other Study ID Numbers: CDR0000287211
NCI-03-C-0109
First Posted: April 9, 2003    Key Record Dates
Last Update Posted: June 20, 2013
Last Verified: August 2006
Keywords provided by National Cancer Institute (NCI):
stage IV melanoma
extraocular extension melanoma
recurrent melanoma
iris melanoma
ciliary body and choroid melanoma, medium/large size
ciliary body and choroid melanoma, small size
recurrent intraocular melanoma
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Aldesleukin
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents