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
16 Years
N/A
Both
Melanoma (Skin)
Trial Information
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
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Clinical response
Safety Issue:
No
Principal Investigator
Steven A. Rosenberg, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
NCI - Surgery Branch
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000486705
NCT ID:
NCT00357461
Start Date:
May 2006
Completion Date:
Related Keywords:
- Melanoma (Skin)
- stage IV melanoma
- recurrent melanoma
- Melanoma
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