Vaccine Therapy With High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma

Sponsor

University of Illinois at Chicago (Other)

Overall Status

Completed

CT.gov ID

NCT00003568

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines may make the body build an immune response that will kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells.

PURPOSE: Randomized phase II trial to study the effectiveness of vaccine therapy with interleukin-2 in treating patients with metastatic melanoma.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: aldesleukin Biological: gp100 antigen Biological: incomplete Freund's adjuvant	Phase 2

Detailed Description

OBJECTIVES:

Define the antitumor activity of gp100:209-217 (210M), a melanoma peptide derived from gp100 mixed with Montanide ISA-51, in combination with high-dose interleukin-2 (IL-2) administered by various schedules in patients with advanced melanoma.
Examine the effect of the addition of gp100:209-217 (210M) peptide vaccine to high-dose IL-2 on the toxicity of the treatment in these patients.
Define the induction of T-cell responses to gp100:209-217 (210M) peptide and its gp100 (parent) protein by ELISA with interferon gamma production or CTL precursor frequencies in these patients after the initial course of treatment.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior therapy (adjuvant interferon vs chemotherapy for advanced disease vs both vs none), ECOG performance status (0 vs 1), and number of organ sites involved (1 vs more than 1). Patients are randomized into 1 of 3 treatment arms. (Arm III closed to accrual as of 11/30/1998.)

Arm I: Patients receive vaccination comprising gp100:209-217 (210M) peptide mixed with Montanide ISA-51 subcutaneously on days 1, 22, 43, and 64. Patients also receive high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours on days 2-6 and 16-20.
Arm II: Patients receive vaccination as in arm I on days 1, 22, 43, and 64. Patients also receive high-dose IL-2 as in arm I on days 44-48 and 60-64. Patients who demonstrate rapid visible disease progression during the initial 4 weeks of therapy while maintaining good performance status may begin high-dose IL-2 on day 23.
Arm III (closed to accrual as of 11/30/1998): Patients receive vaccination as in arm I on day 1 and then high-dose IL-2 as in arm I on day 2. Patients with nonhematologic toxicity may only receive vaccination on weeks 4, 7, and 10. Other patients may also receive IL-2 beginning on day 2 of each treatment week (4, 7, and 10) for up to 14 doses.

Patients in each arm may receive up to a total of 3 courses of treatment.

Patients are followed until death.

PROJECTED ACCRUAL: Approximately 90 patients (25 patients for arms I and II and 40 patients for arm III [arm III closed to accrual as of 11/30/1998]) will be accrued for this study within 12-18 months.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Trial of a Mutated gp100 Melanoma Peptide (g209-217(210M) With Hight Dose Interleukin-2 (IL-2) in HLA-A2.1+Patients With Metastatic Melanoma

Study Start Date :

Nov 1, 1998

Actual Study Completion Date :

Dec 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed clearly progressive metastatic or unresectable melanoma
Must be HLA-A2.1 positive
Measurable disease
No active brain metastases, leptomeningeal disease, or seizure disorder
More than 4 months since prior definitive therapy (surgery or radiotherapy) for brain metastases and must not have evidence of disease on brain CT scan or MRI
No ascites or pleural effusions

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-1 OR
Karnofsky 80-100%

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 9 g/dL

Hepatic:

Bilirubin no greater than 2.0 mg/dL

Renal:

Creatinine no greater than 1.5 mg/dL OR
Creatinine clearance at least 60 mL/min

Cardiovascular:

No congestive heart failure
No symptoms of coronary artery disease
No serious cardiac arrhythmias
No evidence of prior myocardial infarction on EKG
Normal cardiac stress test required for all patients over 40 years

Pulmonary:

FEV_1 greater than 2.0 liters or at least 75% of predicted
No chronic obstructive pulmonary disease

Other:

HIV negative
No significant systemic infection
No contraindication to use of pressor agents
No history of major psychiatric illness
No other major illness that would significantly increase the risk of immunotherapy
No other active malignancy except surgically cured nonmelanoma skin cancer or carcinoma in situ or stage I carcinoma of the cervix
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior interleukin-2
At least 4 weeks since prior vaccine therapy or other cytokine therapy

Chemotherapy:

One prior chemotherapy regimen allowed
At least 4 weeks since prior chemotherapy (6 weeks for carmustine or lomustine) and recovered

Endocrine therapy:

No concurrent steroids

Radiotherapy:

See Disease Characteristics
No prior radiotherapy to areas of measurable disease unless there has been clearly progressive disease in this site or there is measurable disease outside of areas of prior radiation
At least 2 weeks since prior radiotherapy for local control or palliative therapy and recovered

Surgery:

See Disease Characteristics
Recovered from prior major surgery
No prior organ allografts

Other:

No antihypertensive therapy within 24 hours prior to interleukin-2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-0269
2	University of Illinois at Chicago Health Sciences Center	Chicago	Illinois	United States	60612
3	Loyola University Medical Center	Maywood	Illinois	United States	60153
4	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
5	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
6	Comprehensive Cancer Center at Our Lady of Mercy Medical CenterOur	Bronx	New York	United States	10466
7	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15236
8	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-2516
9	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900