Monoclonal Antibody Therapy and Vaccine Therapy in Treating Patients With Resected Stage III or Stage IV Melanoma

NCT00084656 | Completed Phase 2 Results

• 7 other identifiers: CDR0000365467P30CA076292P30CA014089MCC-15241MDX010-16NCI-6446CA184-016
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines may make the body build an immune response to kill tumor cells. Combining the vaccines with Montanide ISA-51 may cause a stronger immune response and kill more tumor cells. Giving monoclonal antibody therapy together with vaccine therapy may be an effective treatment for stage III or stage IV melanoma. PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with vaccine therapy works in treating patients with resected stage III or stage IV melanoma.

Conditions

Intraocular Melanoma; Melanoma (Skin)

Keywords

stage III melanoma; stage IV melanoma; ciliary body and choroid melanoma, medium/large size; extraocular extension melanoma; iris melanoma; recurrent melanoma; recurrent intraocular melanoma; metastatic intraocular melanoma

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Immune-related Adverse Events (irAEs)

  Percentage of participants who experienced an irAE during the course of the study defined by the induction of Grade 1, Grade 2, or acceptable Grade 3 drug-related irAEs. For the purposes of this trial, acceptable drug-related irAEs are skin-related immune-mediated adverse events \< or = Grade 3 (potentially reversible inflammation \< Grade 4 that can be attributable to a local antitumor reaction that could potentially be a therapeutic response will also be considered an acceptable irAE). Note: The confidence interval was calculated using the Clopper Pearson method

  Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)

• Time to Disease Relapse

  To determine the time (months) from first dose to disease relapse. Time to disease relapse is defined from the start of treatment to the first occurrence of any new lesion (reported by the investigator on physical exam or diagnostic imaging assessments that are attributed to metastatic melanoma) or death. Participants who neither relapse nor died will be censored on the date of their last tumor evaluation. Median estimated using Kaplan-Meier method; A two-sided 95% CI for median in each treatment group was computed via the log-log transformation method.

  up to 3 years

Secondary Outcomes (5)

• Number of Participants With Drug-related irAEs of Any Grade

  Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)

• Immunologic Response to the Dose Regimen

  up to 3 years

• Number of Participants Experiencing Hematology-related Lab Abnormalities

  Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)

• Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities

  Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)

• Time to Disease Relapse

  up to 3 years

Study Arms (1)

Arm 1

EXPERIMENTAL

Biological: ipilimumab; Biological: Tyrosinase/gp100/MART-1 Peptides

Interventions

ipilimumab BIOLOGICAL

IV over 90 mins on day 1, wks 1,9,17,25,33,41,53 Dose: 3 mg/kg (Part I), 10 mg/kg (Part II)

Arm 1

Tyrosinase/gp100/MART-1 Peptides BIOLOGICAL

(All subjects in Part I and HLA-A\*0201 positive subjects only in Part II): SC, day 1 of wks 1,3,5,7,9,11,17, 21,25,33,41,53 Dose: 1 mg peptide emulsified in 1 mL Montanide ISA 51 VG.)

Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed melanoma * Stage III (≥ 3 positive lymph nodes) or stage IV disease * Mucosal or ocular melanoma allowed * Completely resected within the past 6 months * Patients with stage III resected melanoma rendered free of disease may have failed, been ineligible for, or refused prior treatment with interferon alfa * Positive staining of tumor tissue for at least one of the following: * Antibody HMB-45 for gp100 * Antibody HMB-45 for tyrosinase * Antibody HMB-45 for MART-1 * HLA-A\*0201 positive by DNA allele-specific polymerase chain reaction assay PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-1 Life expectancy * At least 6 months Hematopoietic * WBC ≥ 2,500/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hematocrit ≥ 30% * Hemoglobin ≥ 10 g/dL Hepatic * AST ≤ 3 times upper limit of normal (ULN)\* * Bilirubin ≤ ULN\* (\< 3.0 mg/dL for patients with Gilbert's syndrome) * No significant hepatic disease that would preclude study participation * Hepatitis B surface antigen negative * Hepatitis C antibody negative NOTE: \* Unless attributable to disease Renal * Creatinine ≤ 2.0 mg/dL * No significant renal disease that would preclude study participation Cardiovascular * No significant cardiac disease that would preclude study participation Pulmonary * No significant pulmonary disease that would preclude study participation Immunologic * No history of any of the following: * Inflammatory bowel disease or any other autoimmune bowel disease * Systemic lupus erythematosus * Rheumatoid arthritis * Autoimmune ocular disease * No systemic hypersensitivity to Montanide ISA-51 or any vaccine component * No active infection requiring therapy * HIV negative Other * 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 significant gastrointestinal disease that would preclude study participation * No significant psychiatric disease that would preclude study participation * No other medical condition that would preclude study participation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 4 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) * No prior gp100 antigen, MART-1 antigen, or tyrosinase peptide * At least 4 weeks since prior immunotherapy for melanoma and recovered * No other concurrent immunotherapy Chemotherapy * At least 4 weeks since prior chemotherapy for melanoma (6 weeks for nitrosoureas) and recovered * No concurrent chemotherapy Endocrine therapy * At least 4 weeks since prior hormonal therapy for melanoma and recovered * At least 4 weeks since prior systemic, inhaled, or topical corticosteroids * No concurrent systemic, inhaled, or topical corticosteroids Radiotherapy * At least 4 weeks since prior radiotherapy for melanoma and recovered Surgery * See Disease Characteristics * At least 4 weeks since prior surgery for melanoma and recovered Other * No concurrent immunosuppressive agents (e.g., cyclosporine and its analog) * Concurrent analgesic therapy allowed provided the dose is stable for the past 14 days

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, 33612-9497, United States

Location

Related Publications (2)

• Garg SK, Ott MJ, Mostofa AGM, Chen Z, Chen YA, Kroeger J, Cao B, Mailloux AW, Agrawal A, Schaible BJ, Sarnaik A, Weber JS, Berglund AE, Mule JJ, Markowitz J. Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy. Front Immunol. 2020 Feb 25;11:164. doi: 10.3389/fimmu.2020.00164. eCollection 2020.

  PMID: 32161584 DERIVED

• Sarnaik AA, Yu B, Yu D, Morelli D, Hall M, Bogle D, Yan L, Targan S, Solomon J, Nichol G, Yellin M, Weber JS. Extended dose ipilimumab with a peptide vaccine: immune correlates associated with clinical benefit in patients with resected high-risk stage IIIc/IV melanoma. Clin Cancer Res. 2011 Feb 15;17(4):896-906. doi: 10.1158/1078-0432.CCR-10-2463. Epub 2010 Nov 24.

  PMID: 21106722 DERIVED

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

Ipilimumab; Monophenol Monooxygenase

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Catechol Oxidase; Mixed Function Oxygenases; Oxygenases; Oxidoreductases; Enzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: May 31, 2004
• Primary Completion: October 31, 2009
• Study Completion: October 31, 2009
• Last Updated: April 14, 2022
• Results First Posted: April 14, 2022

Record last verified: 2022-04

Locations

US (1)