Trial record 1 of 1 for:    08-C-0162
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Anti-MART-1 F5 Lymphocytes to Treat High-Risk Melanoma Patients

This study has been terminated.
(<11 subjects were enrolled to each Arm)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00706992
First received: June 27, 2008
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

Background:

  • Melanoma antigen recognized by T cells (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 transduced cells (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 human leukocyte antigens (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 National Institutes of Health (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.

Condition Intervention Phase
Melanoma
Biological: ALVAC-MART-1 vaccine
Biological: MART-1:26-35(27L) peptide vaccine
Biological: Aldesleukin
Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes
Biological: incomplete Freund's adjuvant
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transfer of Autologous T Cells Transduced With the Anti-MART-1 F5 T Cell Receptor in High Risk Melanoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Percentage of Participants With Immunologic Response [ Time Frame: 9/24/08-10/9/12 ] [ Designated as safety issue: No ]
    Percentage of participants with an immunologic response of >20 spots/100,000 cells measured by IFN gamma secretion using enzyme linked immunosorbent spot (ELISPOT) assay. This was done using ELISPOT assay which measures immune response at the single cell level.

  • Number of Participants With Adverse Events [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.


Enrollment: 50
Study Start Date: June 2008
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I - Adj-4 A2 F5 cells
Patients receive anti-MART-1 F5 TCR-transduced peripheral blood lymphocytes (PBLs) intravenously (IV) over 20-30 minutes on day 0. 1 x 10e9 to 5 x 10e10 IV.
Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes
Given intravenously (IV)
Experimental: Arm II-Adj-4 A2 F5 cells + MART-1:26-35(27L) Peptide
Patients receive anti-MART-1 F5 TCR-transduced PBLs as in arm I and MART-1:26-35(27L) peptide vaccine emulsified in Montanide ISA-51 subcutaneously (SC) on days 0 and 30. 1 x 10e9 to 5 x 10e10 IV + 1.0 mg peptide subcutaneously.
Biological: MART-1:26-35(27L) peptide vaccine
Given subcutaneously
Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes
Given intravenously (IV)
Biological: incomplete Freund's adjuvant
Given subcutaneously
Experimental: Arm III-Adj-4 A2 F5 cells + SQ IL-2
Patients receive anti-MART-1 F5 TCR-transduced PBLs as in arm I and aldesleukin SC on days 0-4. 1 x 10e9 to 5 x 10e10 IV + IL-2 (based on body weight) 125,000 IU/kg/day subcutaneously.
Biological: Aldesleukin
Given subcutaneously
Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes
Given intravenously (IV)
Experimental: Arm IV-Adj-4 A2 F5 cells + MART-1:26-35(27L) Peptide+SQ IL-2
Patients receive anti-MART-1 F5 TCR-transduced PBLs as in arm I, MART-1:26-35(27L) peptide vaccine emulsified in Montanide ISA-51 as in arm II, and aldesleukin as in arm III. 1 x 10e9 to 5 x 10e10 IV + 1.0 mg peptide subcutaneously + IL-2 (based on body weight) 125,000 IU/kg/day subcutaneously.
Biological: MART-1:26-35(27L) peptide vaccine
Given subcutaneously
Biological: Aldesleukin
Given subcutaneously
Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes
Given intravenously (IV)
Biological: incomplete Freund's adjuvant
Given subcutaneously
Experimental: Arm V-Adj-4 A2 F5 cells + ALVAC MART-1:26-35(27L) Vaccine
Patients receive anti-MART-1 F5 TCR-transduced PBLs IV over 20-30 minutes on day 0, and ALVAC-MART-1 vaccine SC on days 0 and 14. 1 x 10e9 to 5 x 10e10 IV + ALVAC vaccine 0.5 ml containing target dose of 10e7 CCID50 (with a range of approximately 10^6.4 to 10^7.9/mL subcutaneously (total of 4 x 10e7 CCID50/2 mL).
Biological: ALVAC-MART-1 vaccine
Given subcutaneously
Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes
Given intravenously (IV)
Experimental: Arm VI-Adj-4 A2 F5 cells + ALVAC MART-1 VAccine + SQ IL-2
Patients receive anti-MART-1 F5 TCR-transduced PBLs and ALVAC-MART-1 vaccine as in arm V, and low-dose aldesleukin SC on days 0-4. 1 x 10e9 to 5 x 10e10 IV + ALVAC vaccine 0.5 ml containing target dose of 10e7 CCID50 (with a range of approximately 10^6.4 to 10^7.9/mL subcutaneously (total of 4 x 10e7 CCID50/2 mL)+ 125,000 IU/kg/day subcutaneously.
Biological: ALVAC-MART-1 vaccine
Given subcutaneously
Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes
Given intravenously (IV)
Experimental: Arm VII-Adj-4 A2 ALVAC MART-1:26-35(27L) Vaccine
Patients receive ALVAC-MART-1 vaccine SC on days 0 and 14. ALVAC vaccine 0.5 ml containing target dose of 10e7 CCID50 (with a range of approximately 10^6.4 to 10^7.9/mL subcutaneously (total of 4 x 10e7 CCID50/2 mL).
Biological: ALVAC-MART-1 vaccine
Given subcutaneously
Biological: Aldesleukin
Given subcutaneously
Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes
Given intravenously (IV)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. 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 National Institutes of Health (NIH) (Department of Anatomic Pathology), and if the diagnosis is not confirmed, the patient will be excluded from the study.
    2. Human leukocyte antigens (HLA-A) 0201 positive.
    3. Age greater than or equal to18 years.
    4. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
    5. Able to understand and sign the Informed Consent Document.
    6. 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
    7. Patients may have had prior adjuvant treatment with immunotherapy, including interferon, as long as 3 weeks have elapsed since prior systemic therapy.
    8. Serology:

      1. Seronegative for human immunodeficiency virus (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).
    9. Hematology:

      1. Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
      2. White blood cell (WBC) (greater than 3000/mm^3).
      3. Platelet count greater than 90,000/mm^3.
      4. Hemoglobin greater than 8.0 g/dl.
    10. Chemistry:

      1. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (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:

  1. Ocular or mucosal melanoma.
  2. 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.
  3. Have autoimmune disease (such as autoimmune colitis or Crohn's disease) or any known immunodeficiency disease, as evidenced by abnormal white blood count (WBC) count.
  4. Concurrent systemic steroid therapy.
  5. Known systemic hypersensitivity to any of the vaccine components, including egg products or Neomycin.
  6. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
  7. 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).
  8. Previous immunization with melanoma antigen recognized by T cells (MART-1).
  9. Known hypersensitivity to any of the agents used in this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00706992

Locations
United States, Maryland
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Rosenberg, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00706992     History of Changes
Other Study ID Numbers: 080162, 08-C-0162
Study First Received: June 27, 2008
Results First Received: December 18, 2012
Last Updated: February 6, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
MART-1 Peptide
Melanoma
Adjuvant Therapy
Gene Therapy
T Cell Persistence

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Freund's Adjuvant
Aldesleukin
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 20, 2014