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

Melanoma (Skin) Clinical Trial

Official title:

Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00085462
• Other study ID #: 040181
• Secondary ID: 04-C-0181NCI-647
• Status: Completed
• Phase: Phase 1
• First received: June 10, 2004
• Last updated: June 21, 2012
• Start date: May 2004
• Est. completion date: September 2008

Study information

• Verified date: June 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00082264

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: September 2008
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• aldesleukin

• filgrastim

• gp100-fowlpox vaccine

• therapeutic autologous lymphocytes

• therapeutic tumor infiltrating lymphocytes

Drug:
• cyclophosphamide

• fludarabine phosphate

Locations

Country	Name	City	State
United States	NCI - Surgery Branch	Bethesda	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,