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

National Institutes of Health Clinical Center (CC)

Status and phase

Completed

Phase 1

Conditions

Melanoma (Skin)

Treatments

Biological: aldesleukin

Biological: gp100-fowlpox vaccine

Biological: therapeutic tumor infiltrating lymphocytes

Drug: cyclophosphamide

Biological: filgrastim

Drug: fludarabine phosphate

Biological: therapeutic autologous lymphocytes

Study type

Interventional

Funder types

NIH

Identifiers

NCT00085462

040181

NCI-6470

CDR0000370798

04-C-0181

Details and patient eligibility

About

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.

Full 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.

Enrollment

61 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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