Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy and Interleukin-12 With or Without Interleukin-2 in Treating Patients With Metastatic Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	UCCRC-11447A NCI-1330, NCT00064168, 1330

Objectives

1. Compare peptide-interferon-gamma production by CD8+ T cells in patients with metastatic melanoma immunized with MAGE-3, Melan-A, gp100 antigen, and NA17-A peptide-pulsed autologous peripheral blood mononuclear cells and interleukin-12 with or without low-dose interleukin-2.
2. Compare the clinical response rate (complete and partial response) in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed melanoma
  • Evidence of metastatic disease by radiological or physical examination
  • In-transit metastases allowed



• HLA-A2 positive



• No untreated brain metastases
  • Brain lesions successfully treated by stereotactic radiotherapy or surgery with no recurrence at 28-day follow-up are allowed

Prior/Concurrent Therapy:

Biologic therapy

• More than 4 weeks since prior biologic therapy
• No prior melanoma vaccine therapy containing the same MAGE-3, Melan-A, gp100 antigen, or NA17 peptides used in the study

Chemotherapy

• Prior chemotherapy allowed

Endocrine therapy

• No concurrent systemic corticosteroids except physiologic replacement doses

Radiotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics

Other

• No concurrent immunosuppressive drugs (e.g., cyclosporine)

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Hemoglobin at least 9 g/dL
• Platelet count at least 100,000/mm³

Hepatic

• SGPT no greater than 2 times upper limit of normal (ULN)
• Bilirubin no greater than 1.5 times ULN
• Lactic dehydrogenase less than 1.25 times ULN
• Hepatitis B and C negative

Renal

• Creatinine no greater than 1.5 times ULN
• Calcium no greater than 11 mg/dL

Cardiovascular

• No significant cardiovascular disease
• No cardiac arrhythmia requiring medical intervention

Immunologic

• HIV negative
• No intrinsic immunosuppression
• No serious concurrent infection, including active tuberculosis
• No prior or active autoimmune disease including:
  • Rheumatoid arthritis (rheumatoid factor-positive with current or recent flare)
  • Inflammatory bowel disease
  • Systemic lupus erythematosus
    • Clinical evidence and antibody titer at least 1:80
  • Ankylosing spondylitis
  • Scleroderma
  • Multiple sclerosis
  • Autoimmune hemolytic anemia
  • Immune thrombocytopenic purpura

Other

• Not pregnant or nursing
• Negative pregnancy test
• No psychiatric illness that would preclude study compliance or giving informed consent
• No active gastrointestinal bleeding
• No uncontrolled peptic ulcer disease

Expected Enrollment

A total of 36 patients (18 per treatment arm) will be accrued for this study within 1.25 years.

Outcomes

Amount of peptide-IFN-γ production by CD8+ T cells at baseline and after completion of study treatment
Quantitation of specific T cells as assessed by peptide/major histocompatibility complex tetramers and flow cytometry at baseline and after every 3 courses
Melanoma antigen gene expression as assessed by reverse-transcriptase polymerase chain reaction (RT-PCR) at baseline, every 3 courses, and after completion of study treatment
Tumor biopsies as assessed by RT-PCR, immunohistochemistry, and gene array analysis at baseline, every 3 courses, and after completion of study treatment

Clinical response rate (complete and partial)
Tumor regression

Outline

This is a randomized, open-label study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive immunization comprising MAGE-3, Melan-A, gp100 antigen, and NA17-A peptide-pulsed autologous peripheral blood mononuclear cells subcutaneously (SC) on day 1 and interleukin-12 (IL-12) SC on days 1, 3, and 5.



• Arm II: Patients receive immunization and IL-12 as in arm I and low-dose interleukin-2 SC on days 7-18.

Treatment in both arms repeats every 21 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving an objective response or stable disease may receive additional treatment sets of 3 courses for up to a total of 9 courses.

Patients are followed every 8 weeks until disease progression and then at least every 3 months thereafter.

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Thomas Gajewski, MD, PhD, Protocol chair		Ph: 773-702-4601; 888-824-0200 Email: tgajewsk@medicine.bsd.uchicago.edu

Registry Information
Official Title		Randomized Phase II Study Of Immunization With mage-3/Melan-A/gp100/NA17 Peptide-Pulsed Autologous PBMC And rhIL-12 With Or Without Low Dose IL-2 In Patients With Metastatic Melanoma
Trial Start Date		2003-07-28
Registered in ClinicalTrials.gov		NCT00064168 1
Date Submitted to PDQ		2003-05-22
Information Last Verified		2006-12-05
NCI Grant/Contract Number		CA14599

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00064168