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

A Phase I/II Trial of a Human Anti-Idiotypic Monoclonal Antibody Vaccine (4B5) Which Mimics the GD2 Antigen, in Patients With Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: sargramostim; Drug: alum adjuvant; Biological: monoclonal antibody 4B5 anti-idiotype vaccine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: sargramostim; Biological: monoclonal antibody 4B5 anti-idiotype vaccine
Experimental: 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.	Drug: alum adjuvant; Biological: monoclonal antibody 4B5 anti-idiotype vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	Baseline to last dose of study drug

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Donald M. Miller, MD, PhD, James Graham Brown Cancer Center at University of Louisville

Study record dates

Study Major Dates

• Study Start: August 1, 1998
• Primary Completion (Actual): June 1, 2001
• Study Completion (Actual): June 1, 2001

Study Registration Dates

• First Submitted: January 21, 2000
• First Submitted That Met QC Criteria: September 15, 2004
• First Posted (Estimate): September 16, 2004

Study Record Updates

• Last Update Posted (Estimate): April 12, 2013
• Last Update Submitted That Met QC Criteria: April 11, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; stage III melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Antacids; Antibodies; Antibodies, Monoclonal; Sargramostim; Aluminum Hydroxide; Aluminum sulfate
• Other Study ID Numbers: CDR0000067424; UAB-9746; UAB-F980729009; NCI-G99-1644