Protocol Number: 08-C-0162

Title:

Transfer of Autologous T Cells Transduced with the Anti-MART-1 F5 T Cell Receptor in High Risk Melanoma

Number:

08-C-0162

Summary:

Background:

-MART-1 is a gene that is present in melanoma cells.

-This study tests an experimental treatment that uses the patient's own lymphocytes (type of white blood cell), which are specially selected and genetically modified with a gene called anti-MART-1 F5 to target and destroy their tumor. Some of the cells are given as an infusion and others are given as a vaccine.

-The anti-MART-1 F5 cells are currently being studied in other patients in combination with chemotherapy and IL-2 (aldesleukin) therapy.

Objectives:

-To determine if the anti-MART-1 F5 treatment can improve the immune system's ability to shrink tumors and to prevent melanoma from recurring.

Eligibility:

-Patients 18 years of age and older whose melanoma has been removed and are currently disease-free, but who are at risk for recurrence.

-Patients who do not have ocular or mucosal melanoma.

-Patients with tissue type HLA-A*0201.

Design:

-Workup: Patients have scans, x-rays, laboratory tests, other tests as needed and leukapheresis, a procedure for collecting white cells to modify in the laboratory and later reinfuse into the patient.

-Patients are assigned to one of four study groups:

--Group 1 receives anti-MART-1 F5 cells by 30-minute infusion through a vein on day 0.

--Group 2 receives anti-MART-1 F5 cells on day 0 followed by injections of MART-1 vaccine, which contains MART-1 and an oil-based liquid called Montanide ISA-51 VG. The vaccine is repeated on day 30.

--Group 3 receives anti-MART-1 F5 cells on day 0 followed by injections of low-dose IL-2 for 5 days (days 0-4).

--Group 4 receives anti-MART-1 F5 cells on day 0 followed by MART-1 vaccine and low-dose IL-2 for 5 days. The vaccine is repeated on day 30.

-Recovery: Patients are monitored closely and given medicines to prevent or treat any side effects of therapy.

-Leukapheresis: Patients undergo leukapheresis at 1 and 3 months after therapy to collect cells to examine the effects of the treatment on the immune system.

-Follow-up: Patients return to NIH 35 days after completing treatment and then at 3 months and every 6 months thereafter for evaluation with a physical examination, review of side effects, laboratory tests and scans. They have blood tests at 3, 6 and 12 months after treatment and then once a year after that. A biopsy may be requested after treatment ends to examine the effects of treatment on the immune system. All patients return to NIH for a physical examination once a year for 5 years and then complete a follow-up questionnaire for another 10 years.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

a. Primary melanomas with lesions that are ulcerated and greater than or equal to 2.0 mm, or any lesions that are greater than or equal to 4.0 mm in thickness, or greater than or equal to 1 positive lymph node, or local recurrence, or resected metastatic disease, within 6 months of surgical resection will be considered. Patients must be clinically disease free at the time of protocol entry as documented by radiologic studies within 6 weeks of patient entry. Patients must have pathologic confirmation of cutaneous melanoma, with slides reviewed at NIH (Department of Anatomic Pathology), and if the diagnosis is not confirmed, the patient will be excluded from the study.

b. HLA-A 0201 positive.

c. Age greater than or equal to18 years.

d. Clinical performance status of ECOG 0 or 1.

e. Able to understand and sign the Informed Consent Document.

f. Patients of both genders must be willing to practice effective birth control during this trial because the potential for teratogenic effects are unknown. Effective birth control requires use of an effective method from the following list: Abstinence, Intrauterine device (IUD); Hormonal (Birth control pills, injections, implants); Tubal ligation; Cervical cap; or Partner's vasectomy

g. Patients may have had prior adjuvant treatment with immunotherapy, including interferon, as long as 3 weeks have elapsed since prior systemic therapy.

h. Serology:

1. Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

2. Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative (The experimental treatment being evaluated in this protocol depends upon an intact immune system and these conditions may have possible immune system effects).

3. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.

i. Hematology:

1. Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim.

2. WBC (greater than 3000/mm(3)).

3. Platelet count greater than 90,000/mm(3).

4. Hemoglobin greater than 8.0 g/dl.

j. Chemistry:

1. Serum ALT/AST less or equal to 2.5 times the upper limit of normal.

2. Serum creatinine less than or equal to 1.6 mg/dl.

3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

EXCLUSION CRITERIA:

a. Ocular or mucosal melanoma.

b. Undergoing or have undergone in the past 3 weeks any systemic therapy except surgery for their cancer, and must have recovered to a grade 1 from any adverse effects of treatment prior to entry, other than those that do not have clinical implications, e.g. vitiligo, alopecia.

c. Have autoimmune disease (such as autoimmune colitis or Crohn's disease) or any known immunodeficiency disease, as evidenced by abnormal WBC count.

d. Concurrent systemic steroid therapy.

e. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.

f. Have active systemic infections including concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).

g. Previous immunization with MART-1.

h. Known hypersensitivity to any of the agents used in this study.

Special Instructions:

Currently Not Provided

Keywords:

MART-1 Peptide

Melanoma

Adjuvant Therapy

Gene Therapy

T Cell Persistence

Recruitment Keyword(s):

Melanoma

Condition(s):

Melanoma

Investigational Drug(s):

PG13/F5af2aB C162D1

MART-1: 26-35(27L)

Montanide ISA-51 VG

Investigational Device(s):

None

Intervention(s):

Genetic: anti MART-1 F5 TCR PBL

Biological/Vaccine: MART-1:26-35(27L)

Drug: Aldesleukin

Drug: PG13/F5af2aB C162D1

Drug: MART-1: 26-35(27L)

Drug: Montanide ISA-51 VG

Supporting Site:

National Cancer Institute

Contact(s):

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
Phone: (866) 820-4505
Fax: (301) 451-1927
Electronic Address: ncisbirc@mail.nih.gov

Citation(s):

Schwartz RH. T cell clonal anergy. Curr Opin Immunol. 1997 Jun;9(3):351-7.

Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004 Sep; 10(9):909-15.

Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 25;298(5594):850-4. Epub 2002 Sep 19.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 01/30/2009