Ipilimumab With or Without Vaccine Therapy in Treating Patients With Previously Treated Stage IV Melanoma

May 14, 2013 updated by: Bristol-Myers Squibb

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Clinical response

Secondary Outcome Measures

Outcome Measure
Response rate
Overall survival
Safety and toxicity
Immunologic response

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Study Registration Dates

First Submitted

July 26, 2006

First Submitted That Met QC Criteria

July 26, 2006

First Posted (Estimate)

July 27, 2006

Study Record Updates

Last Update Posted (Estimate)

May 15, 2013

Last Update Submitted That Met QC Criteria

May 14, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000486705
  • NCI-06-C-0159
  • NCI-P6951
  • MDX-NCI-06-C-0159

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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