Biological Therapy in Treating Patients With Metastatic Melanoma

Melanoma (Skin) Clinical Trial

Official title:

Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD4+ Antigen-Specific T Cell Clones for Patients With Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00045357
• Other study ID #: 1585.00
• Secondary ID: FHCRC-1585.00NCI
• Status: Completed
• Phase: Phase 1
• First received: September 6, 2002
• Last updated: September 20, 2010
• Start date: November 2001
• Est. completion date: August 2008

Study information

• Verified date: September 2010
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Biological therapies use different ways to stimulate the immune system and stop tumor cells from growing. Treating a person's white blood cells in the laboratory and reinfusing them may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma.

Description:

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of autologous CD4+ antigen-specific T-cells for cellular adoptive immunotherapy in patients with metastatic melanoma.

• Determine the safety and toxicity of this regimen in these patients.

• Determine the duration of in vivo persistence of adoptively transferred CD4+ antigen-specific T-cell clones in these patients.

Secondary

• Determine the antitumor effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients undergo leukapheresis to collect peripheral blood mononuclear cells. CD4+ antigen-specific T-cell clones are generated over the next 2-3 months using immunogenic peptides MART1, tyrosinase, or gp100.

Patients receive autologous CD4+ antigen-specific T-cells IV over 30 minutes.

Cohorts of 3-6 patients receive escalating doses of autologous CD4+ antigen-specific T-cells 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.

Patients are followed on days 1 and 3 post T-cell infusion, and then once weekly for 12 weeks.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma

• HLA type expressing one of the following class II alleles:

• DRB1*0401

• DRB1*0404

• DRB1*1501

• DPB1*0401

• DPB1*0402

• Tumor expresses tyrosinase

• Tumor expressing NY-ESO-1 and are HLA type DP4, DP2, or DR7 allowed

• No CNS metastases

• Prior CNS involvement allowed provided there is no evidence of CNS disease at least 2 months after treatment

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 16 weeks

Hematopoietic

• WBC greater than 4,000/mm^3

• Absolute neutrophil count greater than 2,000/mm^3

• Platelet count greater than 100,000/mm^3

• Hematocrit greater than 30%

Hepatic

• SGOT no greater than 3 times upper limit of normal

• INR no greater than 1.5 due to hepatic dysfunction

• No significant hepatic dysfunction, defined as hepatic toxicity grade 2 or greater

Renal

• Creatinine no greater than 2.0 mg/dL OR

• Creatinine clearance at least 60 mL/min

• Calcium no greater than 12 mg/dL

Cardiovascular

• No significant cardiac abnormalities*, defined by any 1 of the following:

• Congestive heart failure

• Clinically significant hypotension

• Symptoms of coronary artery disease

• Cardiac arrhythmias present on EKG requiring drug therapy NOTE: *Patients with a history of cardiovascular disease or any of the above abnormalities undergo a cardiac evaluation, including a cardiac stress test and/or echocardiogram

Pulmonary

• No clinically significant pulmonary dysfunction

• FEV1 at least 1.0 L OR

• FEV1 at least 60%

• DLCO at least 55% (corrected for hemoglobin)

Immunologic

• No acquired or hereditary immunodeficiency

• No autoimmune disease

• No active infection

• No oral temperature greater than 38.2 degrees C within the past 72 hours

• No systemic infection requiring chronic maintenance or suppressive therapy

• HIV negative

Other

• No retinitis or choroiditis

• No history of seizures

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No other concurrent immunotherapy (e.g., interleukins, interferons, melanoma vaccines, IV immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer therapy)

Chemotherapy

• At least 4 weeks since prior chemotherapy (standard or experimental) and recovered

Endocrine therapy

• No concurrent systemic steroids except for toxicity management

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• At least 4 weeks since prior immunosuppressive therapy

• More than 4 weeks since prior experimental drugs and recovered

• No concurrent pentoxifylline

• No other concurrent investigational agents

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• therapeutic autologous lymphocytes

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,