Ipilimumab With or Without Vaccine Therapy in Treating Patients With Previously Treated Stage IV 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. Identifier: NCT00357461
Recruitment Status : Withdrawn
First Posted : July 27, 2006
Last Update Posted : May 15, 2013
National Cancer Institute (NCI)
Information provided by:
Bristol-Myers Squibb

Brief Summary:

RATIONALE: Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Vaccines made from gp100 peptides may help the body build an effective immune response to kill tumor cells. Giving ipilimumab together with vaccine therapy may be an effective treatment for melanoma.

PURPOSE: This randomized phase II trial is studying ipilimumab and vaccine therapy to see how well they work compared to ipilimumab alone in treating patients with previously treated stage IV melanoma.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: gp100:209-217(210M) peptide vaccine Biological: gp100:280-288(288V) peptide vaccine Biological: incomplete Freund's adjuvant Biological: ipilimumab Phase 2

Detailed Description:



  • Compare the impact of ipilimumab with vs without gp100 peptides emulsified with Montanide ISA-51 on clinical response in patients with previously treated, HLA-A*0201 positive stage IV melanoma.


  • Compare the safety/toxicity profile of these regimens in these patients.
  • Determine the immunologic response, as measured by in vitro assays using peripheral blood samples, in patients treated with these regimens.
  • Determine the response rate after a re-induction regimen for patients who have relapsed after initial response.
  • Determine overall survival.

OUTLINE: This is a randomized, open-label study. Patients are stratified according to ECOG performance status (0 vs 1 or 2) and metastases (M1a vs M1 b or M1c). Patients are randomized to 1 of 2 treatment arms.

  • Induction phase:

    • Arm I: Patients receive ipilimumab IV over 90 minutes on day 1.
    • Arm II: Patients receive ipilimumab as in arm I. Patients also receive gp100 peptides emulsified in Montanide ISA-51 subcutaneously (SC) on day 1.

In both arms, treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or better for 12 weeks after 4 courses proceed to maintenance phase.

  • Maintenance phase:

    • Arm I: Patients receive ipilimumab IV over 90 minutes on day 1.
    • Arm II: Patients receive ipilimumab IV as in arm I and gp100 peptides emulsified in Montanide ISA-51 SC on day 1.

Treatment in both arms begins in approximately week 21 and repeats every 3 months for 8 courses in the absence of disease progression or unacceptable toxicity. Patients who relapse or progress while on maintenance phase undergo re-induction comprising 4 courses of treatment with ipilimumab with or without gp100 peptides emulsified in Montanide ISA-51 as in induction phase. Patients achieving responding disease (complete response, partial response, or stable disease) for 12 weeks after re-induction proceed to the maintenance phase as above for up to 8 courses of treatment.

After completion of study treatment, patients are evaluated for 3 weeks after the last treatment, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 94 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Fixed Dose Ipilimumab (MDX-010) 10 mg/kg Given Alone or in Combination With Two gp100 Peptides Emulsified With Montanide ISA-51 VG for Previously Treated HLA-A * 0201 Positive Subjects With Stage IV Melanoma
Study Start Date : May 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
Drug Information available for: Ipilimumab
U.S. FDA Resources

Primary Outcome Measures :
  1. Clinical response

Secondary Outcome Measures :
  1. Safety and toxicity
  2. Immunologic response
  3. Response rate
  4. Overall survival

Information from the National Library of Medicine

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


  • Histologically confirmed stage IV melanoma

    • HLA-A*0201 positive disease
  • Previously treated metastatic disease
  • Clinically evaluable and measurable disease
  • No mucosal or ocular melanoma
  • No evidence of active brain metastases


  • ECOG performance status 0-2
  • WBC ≥ 2,500/mm³
  • Absolute neutrophil count ≥ 1,000/mm³
  • Absolute lymphocyte count ≥ 500/mm³
  • Platelet count ≥ 75,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Creatinine < 2.5 mg/dL
  • AST ≤ 2 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
  • Bilirubin normal (< 3.0 mg/dL if Gilbert's syndrome is present)
  • Hepatitis B surface antigen negative
  • HIV negativity
  • No hepatitis C virus antibodies
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other prior malignancy except for any of the following:

    • Adequately treated basal cell or squamous cell skin cancer
    • Superficial bladder cancer
    • Carcinoma in situ of the cervix
    • Any other cancer from which patient has been disease free for > 5 years
  • No active immune-mediated disease requiring active therapy with any form of steroid or immunosuppressive therapy
  • No documented history of any of the following:

    • Inflammatory bowel disease
    • Regional enteritis
    • Connective tissue disorders, such as systemic lupus erythematosus
    • Rheumatoid arthritis
    • Immune-mediated inflammatory eye disease
    • Sjögren's syndrome
    • Inflammatory neurologic disorder, such as multiple sclerosis
    • Any immune-mediated disease that can cause life-threatening symptoms or severe organ/tissue damage, in the opinion of the principal investigator

      • History of vitiligo or immune-mediated thyroiditis allowed
      • Skin rashes associated with previous therapy allowed provided patient has recovered from treatment-related toxicity to < grade 1
  • No active infection
  • No systemic hypersensitivity to any of the study drugs

    • History of local reactions (e.g., delayed hypersensitivity or glaucomatous reactions) to Montanide ISA-51 allowed
  • No underlying medical condition that, in the opinion of the investigator, would preclude study treatment


  • At least 3 weeks since prior systemic treatment (6 weeks for nitrosoureas) and recovered
  • No prior ipilimumab or gp100 vaccines
  • More than 4 weeks since prior steroids
  • No concurrent systemic or topical corticosteroids or immunosuppressive agents (e.g., cyclosporine or chemotherapy agents), including steroid enemas, inhaled steroids, or steroid eye drops

    • Hormone-replacement therapy allowed

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): NCT00357461

Sponsors and Collaborators
Bristol-Myers Squibb
National Cancer Institute (NCI)
Principal Investigator: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch

Publications: Identifier: NCT00357461     History of Changes
Obsolete Identifiers: NCT00325052
Other Study ID Numbers: CDR0000486705
First Posted: July 27, 2006    Key Record Dates
Last Update Posted: May 15, 2013
Last Verified: May 2013

Keywords provided by Bristol-Myers Squibb:
stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Freund's Adjuvant
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic