Gene-Modified White Blood Cells Followed By Interleukin-2 and Vaccine Therapy in Treating Patients With Metastatic Melanoma

NCT ID: NCT00085462

Last Updated: 2012-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2008-09-30

Brief Summary

RATIONALE: Inserting a gene that has been created in the laboratory into a person's white blood cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Vaccines may make the body build an immune response to kill tumor cells. Combining gene-modified white blood cell infusions with interleukin-2 and vaccine therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying how well giving gene-modified white blood cells when given together with interleukin-2 and vaccine therapy works in treating patients with metastatic melanoma.

Detailed Description

OBJECTIVES:

Primary

• Determine, preliminarily, any clinical tumor regression in lymphodepleted patients with metastatic melanoma treated with fowlpox gp100 antigen immunization and antitumor antigen T-cell receptor (TCR)-engineered tumor infiltrating lymphocytes or CD8+ autologous peripheral blood lymphocytes followed by interleukin-2.

Secondary

• Determine the in vivo survival of TCR gene-engineered cells in patients treated with this regimen.

OUTLINE: Patients are stratified according to their ability to produce tumor-infiltrating lymphocytes (TIL) (yes vs no).

Patients receive lymphodepleting chemotherapy comprising cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.

• Stratum 1 (TIL): Patients receive TIL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0*.
• Stratum 2 (CD8+peripheral blood lymphocytes [PBL]): Patients receive CD8+PBL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0*.

NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.

Patients in both strata also receive fowlpox-gp100 vaccine (before TIL/PBL infusion) IV over 1-2 minutes on days 0 and 28 and high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours on days 0-4 and days 28-32. Patients also receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover.

Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 6-8 weeks after the last dose of vaccine and high-dose IL-2, patients with stable or responding disease may receive 1 retreatment course.

Responding patients are followed at 1, 3, 6, and 12 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.

Conditions

Melanoma (Skin)

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

aldesleukin

Intervention Type: BIOLOGICAL

filgrastim

Intervention Type: BIOLOGICAL

gp100-fowlpox vaccine

Intervention Type: BIOLOGICAL

therapeutic autologous lymphocytes

Intervention Type: BIOLOGICAL

therapeutic tumor infiltrating lymphocytes

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of melanoma

• Metastatic disease
• Measurable disease
• Refractory to standard therapy, including high-dose interleukin-2 therapy
• HLA-A*0201 positive
• Progressive disease during prior immunization to melanoma antigens OR prior treatment with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) cellular therapy with or without myeloablation allowed provided toxicity resolved to ≤ grade 2 (except vitiligo) AND patient does not require systemic steroids
• No brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 8.0 g/dL
• Lymphocyte count > 500/mm^3
• WBC > 3,000/mm^3
• No coagulation disorders

Hepatic

• AST and ALT < 3 times upper limit of normal (ULN)
• Bilirubin ≤ 2.0 mg/dL (3.0 mg/dL in patients with Gilbert's syndrome)
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative (unless antigen negative)

Renal

• Creatinine ≤ 1.6 mg/dL

Cardiovascular

• LVEF ≥ 45% by cardiac stress test

• No LVEF < 45% in patients ≥ 50 years of age
• No myocardial infarction
• No cardiac arrhythmias
• No symptomatic cardiac ischemia
• No prior EKG abnormalities
• No other major cardiovascular illness

Pulmonary

• FEV_1 ≥ 60% of predicted AND no obstructive or restrictive pulmonary disease
• No symptoms of respiratory dysfunction
• No other major respiratory illness

Immunologic

• HIV negative
• Epstein-Barr virus positive
• No active systemic infections (including opportunistic infections)
• No form of primary (e.g., autoimmune colitis or Crohn's disease) or secondary immunodeficiency (due to chemotherapy or radiotherapy)
• No prior severe immediate hypersensitivity reaction to any of the study agents including eggs
• No other major illness of the immune system

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 month after study participation
• Willing to complete a durable power of attorney (DPA)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• More than 6 weeks since prior MDX-010

Chemotherapy

• Not specified

Endocrine therapy

• See Disease Characteristics
• No concurrent systemic steroid therapy

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 4 weeks since other prior systemic therapy and recovered

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health Clinical Center (CC)

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 Trials Referral Office

Bethesda, Maryland, United States

NCI - Surgery Branch

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

04-C-0181

Identifier Type: -

Identifier Source: secondary_id

NCI-6470

Identifier Type: -

Identifier Source: secondary_id

CDR0000370798

Identifier Type: -

Identifier Source: secondary_id

040181

Identifier Type: -

Identifier Source: org_study_id

NCT00082264

Identifier Type: -

Identifier Source: nct_alias