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


Phase 1
18 Years
N/A
Not Enrolling
Both
Melanoma (Skin)

Thank you

Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Steven A. Rosenberg, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Surgery Branch

Authority:

United States: Food and Drug Administration

Study ID:

040181

NCT ID:

NCT00085462

Start Date:

May 2004

Completion Date:

September 2008

Related Keywords:

  • Melanoma (Skin)
  • recurrent melanoma
  • stage IV melanoma
  • Melanoma

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral OfficeBethesda, Maryland  20892-1182
NCI - Surgery BranchBethesda, Maryland  20892-1201