Interleukin-7 and Vaccine Therapy in Treating Patients With Metastatic Melanoma

NCT ID: NCT00091338

Last Updated: 2015-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31

Brief Summary

RATIONALE: Interleukin-7 may stimulate a person's white blood cells to kill tumor cells. Vaccines made from peptides may make the body build an immune response to kill tumor cells. Combining interleukin-7 with vaccine therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-7 when given with vaccine therapy in treating patients with metastatic melanoma.

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of interleukin-7 (IL-7) when administered with melanoma peptide vaccine emulsified in Montanide ISA-51 in patients with metastatic melanoma.
• Determine the safety of this regimen in these patients.

Secondary

• Determine the biological effects of this regimen on T-cell function and phenotype at various doses and at the optimal biological dose in these patients.
• Determine the pharmacokinetic and pharmacodynamic characteristics of IL-7 in patients treated with this regimen.
• Determine the antitumor effects of IL-7, in terms of a dose-escalation strategy, in these patients.

OUTLINE: This is a dose-escalation study of interleukin-7 (IL-7).

Patients receive IL-7 subcutaneously (SC) on days 0, 3, 6, 9, 12, 15, 18, and 21. Patients also receive melanoma peptide vaccine comprising gp100 antigen and MART-1 antigen emulsified in Montanide ISA-51 SC on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of IL-7 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After the MTD is determined, an additional 13 patients are treated at that dose level.

Patients are followed at 1, 2, and 5 weeks, at 3 and 6 months, and then at 1 year.

PROJECTED ACCRUAL: A total of 3-37 patients will be accrued for this study within 1-12.3 months.

Conditions

Melanoma (Skin)

Study Design

• Primary Study Purpose: TREATMENT

Interventions

MART-1 antigen

Intervention Type: BIOLOGICAL

gp100 antigen

Intervention Type: BIOLOGICAL

incomplete Freund's adjuvant

Intervention Type: BIOLOGICAL

recombinant interleukin-7

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• HLA-A*0201-positive disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3*
• Absolute lymphocyte count ≥ 200/mm^3*
• Platelet count > 100,000/mm^3
• No proliferative hematologic disease NOTE: *For 2 consecutive readings performed on 2 different days

Hepatic

• AST and ALT < 3 times upper limit of normal (ULN)
• PT/PTT ≤ 1.5 times ULN
• Hepatitis B negative

• Positive hepatitis B serology indicative of prior immunization (i.e., positive for antibody against hepatitis B surface antigen AND negative for antibody against hepatitis B core antigen) allowed
• Hepatitis C negative

Renal

• Creatinine ≤ 1.4 mg/dL

Cardiovascular

• Ejection fraction > 45% by MUGA for patients ≥ 50 years of age OR with a history of cardiac disease
• No resting blood pressure > 140/90 mm Hg with standard antihypertensive therapy

Pulmonary

• DLCO/VA and FEV_1 > 50% of predicted on pulmonary function test for smokers OR for patients with clinical evidence of compromised pulmonary function
• No history of severe asthma

Immunologic

• HIV negative
• No history of autoimmune disease
• No splenomegaly

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other medical or psychiatric disease that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• More than 4 weeks since prior cytokines
• No prior allogeneic hematopoietic stem cell transplantation
• No concurrent growth factors
• No concurrent monoclonal antibodies
• No other concurrent immunotherapy
• No other concurrent cytokines
• No other concurrent biologic agents

Chemotherapy

• See Disease Characteristics
• No prior intensive myeloablative chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• More than 2 weeks since prior systemic corticosteroids for more than 72 hours in duration
• No concurrent systemic steroids

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics
• No prior splenectomy
• No prior solid organ transplantation

Other

• More than 4 weeks since prior cytotoxic therapy
• No other concurrent cytotoxic therapy
• No concurrent chronic anticoagulation therapy (e.g., high-dose warfarin, heparin, or aspirin)

• Concurrent low-dose warfarin (1-2 mg) allowed
• No concurrent chronic medication for asthma
• No concurrent immunosuppressive therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Steven A. Rosenberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

NCI - Surgery Branch

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Countries

United States

References

Rosenberg SA, Sportes C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL, Stetler-Stevenson M, Morton KE, Mavroukakis SA, Morre M, Buffet R, Mackall CL, Gress RE. IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother. 2006 May-Jun;29(3):313-9. doi: 10.1097/01.cji.0000210386.55951.c2.

Reference Type: RESULT

PMID: 16699374 (View on PubMed)

Other Identifiers

NCI-04-C-0235

Identifier Type: -

Identifier Source: secondary_id

CDR0000387802

Identifier Type: -

Identifier Source: org_study_id

NCT00088322

Identifier Type: -

Identifier Source: nct_alias