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

Sponsor:	University of Chicago
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00064168

Purpose

RATIONALE: Vaccines 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. Interleukin-2 and interleukin-12 may stimulate a person's white blood cells to kill melanoma cells. Combining vaccine therapy and interleukin-12 with interleukin-2 may be a more effective treatment for metastatic melanoma.

PURPOSE: This randomized phase II trial is studying vaccine therapy, interleukin-12, and interleukin-2 to see how well they work compared to vaccine therapy and interleukin-12 in treating patients with metastatic melanoma.

Condition	Intervention	Phase
Melanoma (Skin)	Biological: MART-1 antigen Biological: NA17-A antigen Biological: aldesleukin Biological: gp100 antigen Biological: recombinant MAGE-3.1 antigen Biological: recombinant interleukin-12 Biological: therapeutic autologous lymphocytes	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Aldesleukin Interleukin-12

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Amount of peptide-IFN-γ production by CD8+ T cells at baseline and after completion of study treatment [ Designated as safety issue: No ]
Quantitation of specific T cells as assessed by peptide/major histocompatibility complex tetramers and flow cytometry at baseline and after every 3 courses [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]
Tumor biopsies as assessed by RT-PCR, immunohistochemistry, and gene array analysis at baseline, every 3 courses, and after completion of study treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical response rate (complete and partial) [ Designated as safety issue: No ]
Tumor regression [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	July 2003

Detailed Description:

OBJECTIVES:

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.
Compare the clinical response rate (complete and partial response) in patients treated with these regimens.

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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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/mm^3
Hemoglobin at least 9 g/dL
Platelet count at least 100,000/mm^3

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

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064168

Locations

United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470

Sponsors and Collaborators

University of Chicago

National Cancer Institute (NCI)

Investigators

Study Chair:

Thomas F. Gajewski, MD, PhD

University of Chicago

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00064168 History of Changes
Other Study ID Numbers:	CDR0000309519, UCCRC-11447A, NCI-1330
Study First Received:	July 8, 2003
Last Updated:	February 6, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Interleukin-12
Aldesleukin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Adjuvants, Immunologic
Immunologic Factors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on February 12, 2012