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

Primary Purpose

Melanoma (Skin)

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
monoclonal antibody 4B5 anti-idiotype vaccine
sargramostim
alum adjuvant
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma (Skin) focused on measuring stage III melanoma, stage IV melanoma, recurrent melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Pathologically proven stage III or IV melanoma at high risk for recurrence following surgical resection The following patients are eligible: Resected satellite or intransit metastasis with no evidence of residual disease OR Resected solitary metastatic lesion(s) with no residual disease OR Metastatic melanoma with measurable disease without noncutaneous lesion(s) greater than 5 cm in diameter OR Stage III disease not eligible for interferon alfa therapy No active CNS disease PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL Renal: BUN less than 30 mg/dL Creatinine less than 2 mg/dL Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception HIV negative No prior or concurrent active peripheral neuropathy No immunodeficiency disorder or immunodeficiency state No other prior or concurrent malignancy, except: Curatively treated basal or squamous cell skin cancer Carcinoma in situ of the cervix No hypersensitivity to GM-CSF, yeast derived products, or any study component PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No concurrent immunotherapy Chemotherapy: At least 6 weeks since prior chemotherapy and recovered No more than 1 prior chemotherapy regimen as adjuvant or for metastatic disease No concurrent chemotherapy Endocrine therapy: At least 2 weeks since prior glucocorticoids No concurrent systemic corticosteroids Radiotherapy: At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: See Disease Characteristics Other: At least 30 days since other prior investigational drugs No concurrent immunosuppressive therapy (e.g., cimetidine) No concurrent chronic antihistamine therapy

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Arm I

    Arm II

    Arm Description

    Patients receive human anti-idiotypic monoclonal antibody vaccine (4B5) in sargramostim (GM-CSF) subcutaneously (SQ) on days 0, 14, 28, and 42. Patients receive GM-CSF alone SQ at vaccination site on days 2, 3, and 4 following immunization.

    Patients receive 4B5 plus alum SQ on days 0, 14, 28, and 42. Cohorts of 5 patients receive treatment every 2 weeks for up to 4 courses in the absence of unacceptable toxicity.

    Outcomes

    Primary Outcome Measures

    Compare AEs and SAES in subjects receiving 4B5 plus adjuvant sargramostim (GM-CSF) to alum in patients with stage III or IV melanoma at high risk for recurrence following surgical resection.

    Secondary Outcome Measures

    Compare the development of humoral and/or cellular anti-idiotypic immune response between arm I and arm II
    Compare if the immune response generated against 4B5 is also directed against the melanoma-associated GD2 antigen between Arm I and Arm II
    Measure the immune response to GD2 between subjects receiving the 4B5 plus adjuvant GM-CSF to subjects receiving 4B5 plus alum

    Full Information

    First Posted
    January 21, 2000
    Last Updated
    April 11, 2013
    Sponsor
    University of Alabama at Birmingham
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00004184
    Brief Title
    Monoclonal Antibody Therapy in Treating Patients With Stage III or Stage IV Melanoma
    Official Title
    A Phase I/II Trial of a Human Anti-Idiotypic Monoclonal Antibody Vaccine (4B5) Which Mimics the GD2 Antigen, in Patients With Melanoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2013
    Overall Recruitment Status
    Completed
    Study Start Date
    August 1998 (undefined)
    Primary Completion Date
    June 2001 (Actual)
    Study Completion Date
    June 2001 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    University of Alabama at Birmingham
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I/II trial to study the effectiveness of monoclonal antibody therapy in treating patients who have stage III or stage IV melanoma at high risk for recurrence following surgery to remove the tumor.
    Detailed Description
    OBJECTIVES: I. Determine the toxicity of the human anti-idiotypic monoclonal antibody vaccine (4B5) plus adjuvant sargramostim (GM-CSF) or alum in patients with stage III or IV melanoma at high risk for recurrence following surgical resection. II. Determine whether 4B5 is associated with the development of humoral and/or cellular anti-anti-idiotypic immune response in these patients. III. Determine whether the immune response generated against 4B5 is also directed against the melanoma-associated GD2 antigen in these patients. IV. Determine whether the 4B5 plus adjuvant GM-CSF or alum can elicit an immune response to GD2 in these patients. OUTLINE: Patients are assigned sequentially to one of two treatment arms. Arm I: Patients receive human anti-idiotypic monoclonal antibody vaccine (4B5) in sargramostim (GM-CSF) subcutaneously (SQ) on days 0, 14, 28, and 42. Patients receive GM-CSF alone SQ at vaccination site on days 2, 3, and 4 following immunization. Arm II: Patients receive 4B5 plus alum SQ on days 0, 14, 28, and 42. Cohorts of 5 patients receive treatment every 2 weeks for up to 4 courses in the absence of unacceptable toxicity. PROJECTED ACCRUAL: A maximum of 50 patients (25 per arm) will be accrued for this study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Melanoma (Skin)
    Keywords
    stage III melanoma, stage IV melanoma, recurrent melanoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm I
    Arm Type
    Experimental
    Arm Description
    Patients receive human anti-idiotypic monoclonal antibody vaccine (4B5) in sargramostim (GM-CSF) subcutaneously (SQ) on days 0, 14, 28, and 42. Patients receive GM-CSF alone SQ at vaccination site on days 2, 3, and 4 following immunization.
    Arm Title
    Arm II
    Arm Type
    Experimental
    Arm Description
    Patients receive 4B5 plus alum SQ on days 0, 14, 28, and 42. Cohorts of 5 patients receive treatment every 2 weeks for up to 4 courses in the absence of unacceptable toxicity.
    Intervention Type
    Biological
    Intervention Name(s)
    monoclonal antibody 4B5 anti-idiotype vaccine
    Intervention Type
    Biological
    Intervention Name(s)
    sargramostim
    Intervention Type
    Drug
    Intervention Name(s)
    alum adjuvant
    Primary Outcome Measure Information:
    Title
    Compare AEs and SAES in subjects receiving 4B5 plus adjuvant sargramostim (GM-CSF) to alum in patients with stage III or IV melanoma at high risk for recurrence following surgical resection.
    Time Frame
    Baseline to last dose of study drug
    Secondary Outcome Measure Information:
    Title
    Compare the development of humoral and/or cellular anti-idiotypic immune response between arm I and arm II
    Time Frame
    baseline to last dose of study drug
    Title
    Compare if the immune response generated against 4B5 is also directed against the melanoma-associated GD2 antigen between Arm I and Arm II
    Time Frame
    baseline through last dose of study drug
    Title
    Measure the immune response to GD2 between subjects receiving the 4B5 plus adjuvant GM-CSF to subjects receiving 4B5 plus alum
    Time Frame
    baseline to survival

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    DISEASE CHARACTERISTICS: Pathologically proven stage III or IV melanoma at high risk for recurrence following surgical resection The following patients are eligible: Resected satellite or intransit metastasis with no evidence of residual disease OR Resected solitary metastatic lesion(s) with no residual disease OR Metastatic melanoma with measurable disease without noncutaneous lesion(s) greater than 5 cm in diameter OR Stage III disease not eligible for interferon alfa therapy No active CNS disease PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL Renal: BUN less than 30 mg/dL Creatinine less than 2 mg/dL Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception HIV negative No prior or concurrent active peripheral neuropathy No immunodeficiency disorder or immunodeficiency state No other prior or concurrent malignancy, except: Curatively treated basal or squamous cell skin cancer Carcinoma in situ of the cervix No hypersensitivity to GM-CSF, yeast derived products, or any study component PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No concurrent immunotherapy Chemotherapy: At least 6 weeks since prior chemotherapy and recovered No more than 1 prior chemotherapy regimen as adjuvant or for metastatic disease No concurrent chemotherapy Endocrine therapy: At least 2 weeks since prior glucocorticoids No concurrent systemic corticosteroids Radiotherapy: At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: See Disease Characteristics Other: At least 30 days since other prior investigational drugs No concurrent immunosuppressive therapy (e.g., cimetidine) No concurrent chronic antihistamine therapy
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Donald M. Miller, MD, PhD
    Organizational Affiliation
    James Graham Brown Cancer Center at University of Louisville
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

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

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