Vaccine Therapy and Interleukin-12 in Treating Patients With Metastatic Melanoma

Phase I/II Study of Immunization With MAGE-3 Peptide-Pulsed Autologous PBMC Plus rhIL-12 in Patients With Metastatic Melanoma

RATIONALE: Vaccines made from a tumor antigen gene may make the body build an immune response to kill tumor cells. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cell to kill melanoma cells. Combining vaccine therapy with interleukin-12 may kill more melanoma cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy plus interleukin-12 in treating patients who have metastatic melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: MART-1 antigen; Biological: recombinant MAGE-3.1 antigen; Biological: recombinant interleukin-12

Detailed Description

OBJECTIVES: I. Determine the safety and maximum tolerated dose level of the vaccine consisting of MAGE-3 or Melan-A (human tumor antigen genes) peptide-pulsed autologous peripheral blood mononuclear cells plus interleukin-12. II. Determine if the procedure results in successful immunization. III. Assess the response of the tumor to the vaccine.

OUTLINE: This is an open label, nonrandomized, single institution study. Patients receive 3 initial courses of treatment consisting of 21 days each. Treatment consists of an immunization with MAGE-3 or Melan-A peptide-loaded autologous PBMC and interleukin-12 (IL-12) on the first day, IL-12 on days 3 and 5, and 16 days of rest. The first cohort is not administered IL-12 and the next cohorts are given escalating doses of IL-12. The Phase II dose will be one dose level below the MTD. Patients who have a tumor remission response or stable disease may continue treatment for up to one year. Phase I completed as of 04/1999. Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histologically confirmed metastatic melanoma Patient must express HLA-A2 (a human leukocyte antigen) Tumor must express MAGE-3 or Melan-A by polymerase chain reaction (PCR) analysis No untreated brain metastases

PATIENT CHARACTERISTICS: Age: Not specified Performance status: Karnofsky 70%-100% Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater 1.5 times upper limit of normal (ULN) SGPT no greater than 2 times ULN Renal: Calcium no greater than 11 mg/dL Creatinine no greater than 1.5 times ULN Cardiovascular: No significant cardiovascular disease or cardiac arrhythmia requiring medical intervention Other: Hepatitis B surface antigen negative HIV negative No serious concurrent infection No clinically significant autoimmune disease No active gastrointestinal bleeding or uncontrolled peptic ulcer disease No history of inflammatory bowel disease No psychiatric illness that may interfere with compliance in study Not pregnant or nursing

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunosuppressive drugs At least 4 weeks since biologic therapy Chemotherapy: At least 2 weeks since chemotherapy Endocrine therapy: No concurrent systemic corticosteroids (except physiologic replacement doses) Radiotherapy: At least 2 weeks since radiotherapy Surgery: At least 2 weeks since surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Melan-A peptide loaded PBMCs (sc, q3wk x 3), rhIL-12 (4 mcg, sc, days 1, 3 and 5 of every 3 wk cycle)	Biological: MART-1 antigen; Melan-A peptide loaded PBMCs (sc, q3wk x 3); Biological: recombinant MAGE-3.1 antigen; Other Names: Melan-A peptide loaded PBMCs (sc, q3wk x 3); Biological: recombinant interleukin-12; rhIL-12 (4 mcg, sc, days 1, 3 and 5 of every 3 wk cycle)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical Response Rate	4 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Thomas F. Gajewski, MD, PhD, University of Chicago

Study record dates

Study Major Dates

• Study Start: January 1, 1997
• Primary Completion (Actual): August 1, 2002
• Study Completion (Actual): November 1, 2002

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: April 21, 2004
• First Posted (Estimate): April 22, 2004

Study Record Updates

• Last Update Posted (Estimate): September 5, 2013
• Last Update Submitted That Met QC Criteria: September 4, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV 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; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Adjuvants, Immunologic; Interleukin-12
• Other Study ID Numbers: 9018 (Other Identifier: CTEP); UCCRC-9018; UCCRC-8381; NCI-G97-1162