Study Stopped
\<11 subjects were enrolled to each Arm
Anti-MART-1 F5 Lymphocytes to Treat High-Risk Melanoma Patients
Transfer of Autologous T Cells Transduced With the Anti-MART-1 F5 T Cell Receptor in High Risk Melanoma
2 other identifiers
interventional
50
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jun 2008
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2008
CompletedFirst Submitted
Initial submission to the registry
June 27, 2008
CompletedFirst Posted
Study publicly available on registry
June 30, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2012
CompletedResults Posted
Study results publicly available
March 19, 2013
CompletedOctober 28, 2015
October 1, 2015
4.4 years
June 27, 2008
December 18, 2012
October 6, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With Immunologic Response
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.
9/24/08-10/9/12
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
4 years
Study Arms (7)
Arm I - Adj-4 A2 F5 cells
EXPERIMENTALPatients 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.
Arm II-Adj-4 A2 F5 cells + MART-1:26-35(27L) Peptide
EXPERIMENTALPatients 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.
Arm III-Adj-4 A2 F5 cells + SQ IL-2
EXPERIMENTALPatients 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.
Arm IV-Adj-4 A2 F5 cells + MART-1:26-35(27L) Peptide+SQ IL-2
EXPERIMENTALPatients 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.
Arm V-Adj-4 A2 F5 cells + ALVAC MART-1:26-35(27L) Vaccine
EXPERIMENTALPatients 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).
Arm VI-Adj-4 A2 F5 cells + ALVAC MART-1 VAccine + SQ IL-2
EXPERIMENTALPatients 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.
Arm VII-Adj-4 A2 ALVAC MART-1:26-35(27L) Vaccine
EXPERIMENTALPatients 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).
Interventions
Given subcutaneously
Given subcutaneously
Given subcutaneously
Given intravenously (IV)
Given subcutaneously
Eligibility Criteria
You may qualify if:
- 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.
- Human leukocyte antigens (HLA-A) 0201 positive.
- Age greater than or equal to18 years.
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Able to understand and sign the Informed Consent Document.
- 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
- Patients may have had prior adjuvant treatment with immunotherapy, including interferon, as long as 3 weeks have elapsed since prior systemic therapy.
- Serology:
- 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.)
- 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).
- Hematology:
- Absolute neutrophil count greater than 1000/mm\^3 without the support of filgrastim.
- White blood cell (WBC) (greater than 3000/mm\^3).
- Platelet count greater than 90,000/mm\^3.
- Hemoglobin greater than 8.0 g/dl.
- +4 more criteria
You may not qualify if:
- Ocular or mucosal melanoma.
- 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.
- 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.
- Concurrent systemic steroid therapy.
- Known systemic hypersensitivity to any of the vaccine components, including egg products or Neomycin.
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
- 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).
- Previous immunization with melanoma antigen recognized by T cells (MART-1).
- Known hypersensitivity to any of the agents used in this study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (3)
Schwartz RH. T cell clonal anergy. Curr Opin Immunol. 1997 Jun;9(3):351-7. doi: 10.1016/s0952-7915(97)80081-7.
PMID: 9203408BACKGROUNDRosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004 Sep;10(9):909-15. doi: 10.1038/nm1100.
PMID: 15340416BACKGROUNDDudley 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. doi: 10.1126/science.1076514. Epub 2002 Sep 19.
PMID: 12242449BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Steven Rosenberg
- Organization
- National Cancer Institute, National Institutes of Health
Study Officials
- PRINCIPAL INVESTIGATOR
Steven Rosenberg, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 27, 2008
First Posted
June 30, 2008
Study Start
June 1, 2008
Primary Completion
November 1, 2012
Study Completion
November 1, 2012
Last Updated
October 28, 2015
Results First Posted
March 19, 2013
Record last verified: 2015-10