Anti-gp100 Cells Plus ALVAC gp100 Vaccine to Treat Advanced Melanoma
- gp100 is a protein that is often found in melanoma tumors.
- An experimental procedure developed for treating patients with melanoma uses anti-gp100 cells designed to destroy their tumors. The anti-gp100 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) gp100, made from a virus that ordinarily infects canaries and is modified to carry a copy of the gp100 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 gp 100 cells.
-To evaluate the safety and effectiveness of anti-gp100 cells and the ALVAC gp100 vaccine in treating patients with advanced melanoma.
-Patients 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 gp100 cells.
- Patients receive the ALVAC vaccine, anti-gp100 cells and interleukin-2 (IL-2) (an approved treatment for advanced melanoma). The anti gp100 cells are given as an infusion through a vein. The vaccine is given as injections just before the infusion of gp100 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.
Drug: fludarabine phosphate
Biological: ALVAC gp100 Vaccine
Biological: anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Anti-gp100:154-162 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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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: 18.5 months ] [ Designated as safety issue: Yes ]Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
- Number of Participants Who Develop Anti-mouse T Cell Receptor (TCR) Antibodies [ Time Frame: 1 month ] [ Designated as safety issue: No ]Blood samples are collected from the patient and an immunological test is conducted in the laboratory to determine if the patient has generated antibodies against the mouse T-cell receptor which is part of the anti-gp100 cells.
|Study Start Date:||January 2008|
|Study Completion Date:||February 2011|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Experimental: ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2
ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high dose (HD) interleukin-2 (IL-2): ALVAC vaccine 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 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14.
Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)- 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)
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: FludaraBiological: Aldesleukin
720,000 IU/kg intravenously over 15 minutes every 8 hours (+/- 1 hour) for up to 5 days.
Other Name: ProleukinBiological: ALVAC gp100 Vaccine
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 gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL)
Other Name: ALVACBiological: anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL)
3 x 10^11 anti-gp100:154-162 TCR engineered PBL by intravenous infusion. A minimum of approximately 5 x 10^8 cells will be given.
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|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|