Vaccine Therapy With or Without Recombinant Interleukin-12 Followed by Daclizumab in Treating Patients With Metastatic Melanoma

NCT01307618 | Terminated Phase 2 Results

• 7 other identifiers: NCI-2011-02580UCCRC-10-324-BCDR000069623310-324-B8445P30CA014599N01CM00071
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial is studying how well giving vaccine therapy together with or without recombinant interleukin-12 followed by daclizumab works in treating patients with melanoma that has spread to other places in the body. Vaccines made from peptides or antigens may help the body build an effective immune response to kill tumor cells. Recombinant interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating white blood cells to kill melanoma cells. Monoclonal antibodies, such as daclizumab, may decrease the number of regulatory T cells (T cells that suppress the activation of the immmune system) and may lead to a better immune response against melanoma. It is not yet known whether vaccine therapy is more effective with interleukin-12 and daclizumab in treating melanoma.

Conditions

Recurrent Melanoma; Stage IV Skin Melanoma

Outcome Measures

Primary Outcomes (3)

• Frequency of Vaccine-induced CD8+ T Cells Assessed by Enzyme-linked Immunospot (ELISPOT)

  Data before treatment and after 3 vaccines will be assessed using paired t-tests within each cohort as well as a two-sample t-test of the mean post-treatment levels between cohorts. Repeated measures analysis of variance or mixed effects models will be utilized to further characterize changes in the levels of circulating T cells over time.

  Up to 4 years

• Absolute Number of CD4+CD25+FoxP3+ Regulatory T Cells From Peripheral Blood

  Descriptive statistics and paired t-tests will be generated to describe the frequency and absolute number of CD4+CD25+FoxP3+ cells before and after daclizumab, and also at subsequent time points. Repeated measures of analysis of variance and mixed effects models will be used to further evaluate change in numbers over time, and to compare these changes between cohorts.

  Up to 4 years

• Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)

  Up to 4 years

Secondary Outcomes (3)

• Progression-free Survival Assessed by Modified World Health Organization (WHO) Criteria

  Up to 4 years

• Overall Survival Assessed by Modified WHO Criteria

  Up to 4 years

• Gene Expression Profiles

  Up to 4 years

Study Arms (2)

Arm I (vaccine therapy)

EXPERIMENTAL

Patients receive vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 ID or SC on days 1, 22, and 50.

Biological: NA17.A2 Peptide Vaccine; Biological: Recombinant MAGE-3.1 Antigen; Biological: MART-1 Antigen; Other: Laboratory Biomarker Analysis

Arm II (vaccine therapy, IL-12)

EXPERIMENTAL

Patients receive vaccination as in arm I with an admixture of IL-12 ID or SC on days 1, 22, and 50.

Biological: NA17.A2 Peptide Vaccine; Biological: Recombinant MAGE-3.1 Antigen; Biological: Recombinant Interleukin-12; Other: Laboratory Biomarker Analysis

Interventions

NA17.A2 Peptide Vaccine BIOLOGICAL

Given SC or ID

Also known as: NA17.A2

Arm I (vaccine therapy); Arm II (vaccine therapy, IL-12)

Recombinant MAGE-3.1 Antigen BIOLOGICAL

Given SC or ID

Also known as: MAGE-3, MAGE-3.1

Arm I (vaccine therapy); Arm II (vaccine therapy, IL-12)

Recombinant Interleukin-12 BIOLOGICAL

Given SC or ID

Arm II (vaccine therapy, IL-12)

MART-1 Antigen BIOLOGICAL

Given SC or ID

Also known as: Antigen LB39-AA, Antigen SK29-AA, MART-1 Tumor Antigen

Arm I (vaccine therapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (vaccine therapy); Arm II (vaccine therapy, IL-12)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed melanoma with evidence of metastatic disease either by radiologic or physical examination
• In-transit metastases are allowed
• Biopsy should be performed to reconfirm the diagnosis in cases of doubt
• Patients must have measurable disease
• For computed tomography (CT) imaging, this is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
• For cutaneous lesions, these must be measurable with a ruler and documented photographically with a ruler in place
• There are no limits on the number of prior therapies; patients must not have received a vaccine containing any of the melanoma antigen peptides, nor previously received daclizumab; at least 4 weeks must have passed since prior chemotherapy or radiation therapy (6 weeks for BCNU \[carmustine\] or mitomycin C)
• Life expectancy greater than or equal to 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky ≥ 80%)
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Hemoglobin ≥ 9 g/dL
• Platelets ≥ 100,000/mcL
• Creatinine ≤ 1.5 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN

You may not qualify if:

• Patients who have had chemotherapy, biological or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients may not be receiving any other investigational agents
• Presence of untreated brain metastases; all patients must undergo brain imaging as part of the pre-study evaluation; only patients with no brain metastases, or with brain lesions successfully treated by stereotactic radiation or surgical removal without progression at 28-day follow-up and off corticosteroids for 4 weeks, will be eligible
• History of allergic reactions attributed to compounds of similar chemical or biologic composition IL-12 or other agents used in the study
• Concurrent systemic corticosteroids (except physiologic replacement doses) or other immunosuppressive drugs (eg. cyclosporin A)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with IL-12; women of child-bearing age must be tested for urinary or serum beta-human chorionic gonadotropin (HCG)
• Patients with intrinsic immunosuppression, including seropositivity for human immunodeficiency virus (HIV) antibody; patients should be tested for HIV; HIV-positive patients are ineligible
• Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent; patients with clinical evidence of dementia should have a competent designee participate in decision making
• Serious concurrent infection, including active tuberculosis, hepatitis B, or hepatitis C; patients should be tested for hepatitis B surface antigen and hepatitis C antibody; patients who are hepatitis C antibody (Ab) positive can be eligible if they are polymerase chain reaction (PCR)-negative
• Active or history of autoimmune disease including but not limited to: rheumatoid arthritis (rheumatoid factor \[RF\]-positive with current or recent flare), inflammatory bowel disease, systemic lupus erythematosis (clinical evidence with antinuclear antibody \[ANA\] 1:80 or greater), ankylosing spondylitis, scleroderma, multiple sclerosis, autoimmune hemolytic anemia, and immune thrombocytopenic purpura; seropositivity alone will not be considered active autoimmunity; patients with immune-mediated hypothyrodisim and/or vitiligo are allowed
• Active gastrointestinal bleeding or uncontrolled peptic ulcer disease

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

MAGEA3 protein, human; Interleukin-12 Subunit p35; MART-1 Antigen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Interleukin-12; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Melanoma-Specific Antigens; Neoplasm Proteins; Antigens, Neoplasm; Antigens

Results Point of Contact

• Title: Tomas Gajewski
• Organization: University of Chicago Comprehensive Cancer Center

tgajewsk@medicine.bsd.uchicago.edu

773-702-4601

Study Officials

• Thomas Gajewski

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2011
• First Posted: March 3, 2011
• Study Start: February 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: February 1, 2015
• Last Updated: October 24, 2016
• Results First Posted: October 24, 2016

Record last verified: 2016-08

Locations

US (1)