Anti-MART-1 F5 Cells Plus ALVAC MART-1 Vaccine to Treat Advanced Melanoma
- Melanoma antigen recognized by T-cells (MART)-1 is a protein present in melanoma cells.
- An experimental procedure developed for treating patients with melanoma uses the anti-MART-1 F5 gene and a type of virus to make special cells called anti-MART-1 F5 cells that are designed to destroy the patient's tumor. These cells are created in the laboratory using the patient's own tumor cells or blood cells.
- The treatment procedure also uses a vaccine called plaque purified canarypox vector (ALVAC) MART-1, made from a virus that ordinarily infects canaries and is modified to carry a copy of the MART-1 gene. The virus cannot reproduce in mammals, so it cannot cause disease in humans. When the vaccine is injected into a patient, it stimulates cells in the immune system that may increase the efficiency of the anti-MART-1 F5 cells.
-To evaluate the safety and effectiveness of anti-MART-1 F5 and the ALVAC vaccine in treating patients with advanced melanoma.
-Patients 18 years of age with metastatic melanoma for whom standard treatments have not been effective.
- Patients undergo scans, x-rays and other tests and leukapheresis to obtain white cells for laboratory treatment.
- Patients have 7 days of chemotherapy to prepare the immune system for receiving the anti-MART-1 F5.
- Patients receive the ALVAC vaccine, anti-MART-1 F5 cells and interleukin-2 (IL-2) (an approved treatment for advanced melanoma). The anti-MART-1 F5 cells are given as an infusion through a vein. The vaccine is given as injections just before the infusion of anti-MART-1 F5 cells and again 2 weeks later. IL-2 is given as a 15-minute infusion every 8 hours for up to 5 days after the cell infusion for a maximum of 15 doses.
- After hospital discharge, patients return to the clinic for periodic follow-up with a physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.
|Metastatic Melanoma Skin Cancer||Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes Biological: ALVAC MART-1 Vaccine Biological: aldesleukin Drug: cyclophosphamide Drug: fludarabine phosphate||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Anti-MART-1 F5 TCR-Gene Engineered Lymphocytes and ALVAC Virus Immunization|
- Number of Participants With Metastatic Melanoma Who Develop Clinical Tumor Regression (CR or PR) [ Time Frame: 4-6 weeks after treatment and then monthly for approximately 3 to 4 months or until off study criteria are met ]Clinical tumor response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 criteria. Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is a 30% decrease in lesions taking as reference the baseline sum longest diameter (LD). For details about the RECIST criteria see the protocol link module.
- Number of Participants With in Vivo Survival of T-cell Receptor (TCR) Gene-engineered Cells [ Time Frame: 1 month ]T cell receptor (TCR) and vector presence will be quantitated in peripheral blood mononuclear cells (PBMC) samples using established polymerase chain reaction (PCR) techniques. This will provide data to estimate the in vivo survival of lymphocytes derived from the infused cells.
- Number of Participants With Adverse Events [ Time Frame: 15 months ]Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
|Study Start Date:||January 2008|
|Study Completion Date:||March 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
Experimental: ALVAC plus anti-MART-1 F5 TCR PBL + HD IL-2
ALVAC plus anti-MART-1 F5 T cell receptor (TCR ) peripheral blood lymphocytes (PBL) + high dose (HD) interleukin 2 (IL-2): ALVAC vaccine-approximately two hours prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10^7 cell culture infectious dose 50% (CCID50) (with a range of approximately 10^6,4 to 10^7,9/mL) of the MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2 mL). This will be repeated on day 14.
Aldesleukin - 720,000 IU/kg intravenously over 15 minutes every 8 hours (+/- 1 hour) for up to 5 days.
Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes
ALVAC vaccine-approximately two hours prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10^7 CCID50 (with a range of approximately 10^6,4 to 10^7,9/mL) of the MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2 mL). This will be repeated on day 14.Biological: ALVAC MART-1 Vaccine
ALVAC vaccine-approximately two hours prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10^7 CCID50 (with a range of approximately 10^6,4 to 10^7,9/mL) of the MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2 mL). This will be repeated on day 14.Biological: aldesleukin
Aldesleukin - 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)
Other Names:Drug: cyclophosphamide
60 mg/kg day x 2 days intravenous in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg day x 2 days over 1 hour
Other Name: CytoxanDrug: fludarabine phosphate
25 mg/m^2 day intravenous piggy back over 30 minutes for 5 days
Other Name: Fludara
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00612222
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute, National Institutes of Health|