Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00080353
Status:
COMPLETED
Last Update Posted:
2012-06-14
First Post:
2004-03-27
Brief Title:
Vaccine Treatment in Combination With IL-2 and Treated Lymphocytes for Advanced Melanoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase II Study in Metastatic Melanoma Using Lymphocytes Reactive With the gp100 Antigen and Immunization Using a Recombinant rF-gp100P209 Virus Encoding a gp100 Peptide Following a Nonmyeloablative Lymphocyte Depleting Regimen
Status:
COMPLETED
Status Verified Date:
2012-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the effectiveness of treating advanced melanoma with special tumor-fighting cells taken from the patients blood or tumor and grown in the laboratory The cells are given along with infusions of a growth factor-like substance called interleukin-2 IL-2 and an experimental vaccine called fowlpox gp100 This vaccine consists of a peptide part of a protein called gp100 that is often found in melanoma tumors and chicken virus fowlpox that has been altered so that it cannot produce illness in humans
Patients 16 years of age and older with melanoma that has spread beyond the original site and that does not respond to standard treatment may be eligible for this study Candidates are screened with a medical history and physical examination chest x-ray electrocardiogram blood and urine tests and x-rays and scans to the evaluate the extent and size of the tumor Because the experimental preparation is based on tissue type only patients with tissue type HLA-A0201 may participate Tissue type is determined by a blood test
Participants undergo the following procedures
Leukapheresis a procedure for collecting lymphocytes white blood cells Using this procedure special cells with good tumor-fighting ability are selected and removed for later re-infusion into the patient To collect the cells blood is withdrawn through a needle in an arm vein and directed through a catheter into a cell-separating machine The lymphocytes are removed and the rest of the blood is returned to the body through the same needle Alternatively lymphocytes may also be collected from biopsied tumor tissue obtained either with a needle or by a small cut in the tumor
G-CSF injections This growth factor is injected under the skin every day for 5 days to stimulate white blood cell production
Catheter placement Upon admission to the Clinical Center for treatment the patient has a catheter plastic tube placed in a vein in the neck or arm for giving chemotherapy and other medicines for infusing the lymphocytes and for collecting blood samples
Leukapheresis Repeated in the hospital to collect and store blood that may be needed in the rare event that the patients blood components do not recover after chemotherapy
Chemotherapy A week before the lymphocyte infusion patients receive a 1-hour infusion of cyclophosphamide for 2 days and then a 15- to 30-minute infusion of fludarabine for 5 days to suppress the immune system and thereby prevent rejection of the infused lymphocytes
Vaccine and lymphocyte delivery The vaccine is injected through the catheter followed by a 30-minute infusion of the lymphocytes
IL-2 and G-CSF Patients receive IL-2 infusions every 8 hours for up to 5 days after the cell infusion to help keep the cells alive and G-CSF injections under the skin every day after the cell infusion until white cells increase to a sufficient number The entire hospital stay is usually 12 to 16 days
About 4 weeks after the lymphocyte infusion patients are re-admitted to the hospital for about 10 days for a second vaccine injection and course of IL-2 infusions Between 2 and 4 weeks after completing the full treatment regimen patients return to NIH for evaluation Those whose tumors have shrunk or remained stable may repeat the entire treatment regimen two times Those whose tumors continued to grow may be re-treated with infusion of lymphocytes through an artery instead of a vein if their tumors receive blood from a major artery If this is not feasible or if it is tried without success the patients will be taken off the study
Patients 16 years of age and older with melanoma that has spread beyond the original site and that does not respond to standard treatment may be eligible for this study Candidates are screened with a medical history and physical examination chest x-ray electrocardiogram blood and urine tests and x-rays and scans to the evaluate the extent and size of the tumor Because the experimental preparation is based on tissue type only patients with tissue type HLA-A0201 may participate Tissue type is determined by a blood test
Participants undergo the following procedures
Leukapheresis a procedure for collecting lymphocytes white blood cells Using this procedure special cells with good tumor-fighting ability are selected and removed for later re-infusion into the patient To collect the cells blood is withdrawn through a needle in an arm vein and directed through a catheter into a cell-separating machine The lymphocytes are removed and the rest of the blood is returned to the body through the same needle Alternatively lymphocytes may also be collected from biopsied tumor tissue obtained either with a needle or by a small cut in the tumor
G-CSF injections This growth factor is injected under the skin every day for 5 days to stimulate white blood cell production
Catheter placement Upon admission to the Clinical Center for treatment the patient has a catheter plastic tube placed in a vein in the neck or arm for giving chemotherapy and other medicines for infusing the lymphocytes and for collecting blood samples
Leukapheresis Repeated in the hospital to collect and store blood that may be needed in the rare event that the patients blood components do not recover after chemotherapy
Chemotherapy A week before the lymphocyte infusion patients receive a 1-hour infusion of cyclophosphamide for 2 days and then a 15- to 30-minute infusion of fludarabine for 5 days to suppress the immune system and thereby prevent rejection of the infused lymphocytes
Vaccine and lymphocyte delivery The vaccine is injected through the catheter followed by a 30-minute infusion of the lymphocytes
IL-2 and G-CSF Patients receive IL-2 infusions every 8 hours for up to 5 days after the cell infusion to help keep the cells alive and G-CSF injections under the skin every day after the cell infusion until white cells increase to a sufficient number The entire hospital stay is usually 12 to 16 days
About 4 weeks after the lymphocyte infusion patients are re-admitted to the hospital for about 10 days for a second vaccine injection and course of IL-2 infusions Between 2 and 4 weeks after completing the full treatment regimen patients return to NIH for evaluation Those whose tumors have shrunk or remained stable may repeat the entire treatment regimen two times Those whose tumors continued to grow may be re-treated with infusion of lymphocytes through an artery instead of a vein if their tumors receive blood from a major artery If this is not feasible or if it is tried without success the patients will be taken off the study
Detailed Description:
Background
Recent clinical studies in the Surgery Branch have demonstrated clinical responses in patients undergoing adoptive transfer of autologous tumor reactive lymphocytes following a non-myeloablative immunosuppressive chemotherapy regimen Additional studies in the Surgery Branch using immunization with recombinant fowlpox virus after cell transfer in the immunosuppressed host have provided strong evidence to suggest that the adoptive transfer of lymphocytes in our clinical protocols in patients with melanoma will be substantially improved by the simultaneous administration of recombinant fowlpox virus
Objectives
The primary objective will be to determine whether gp100 reactive lymphocytes infused in conjunction with immunization with rf-gp100P209 and administration of high dose or low dose IL-2 may result in complete clinical tumor regression in patients with metastatic melanoma receiving a nonmyeloablative but lymphoid depleting preparative regimen Secondary objectives will be to determine the survival in patients of infused cells following this regimen and to determine the safety of this regimen
Eligibility
Patients who are HLA-A201 must be greater than or equal to 16 years of age and have measurable metastatic melanoma that is refractory to standard therapy Safety laboratory values must be within defined parameters More than four weeks must have elapsed since any prior systemic therapy Patients must be eligible to receive IL-2 and may not have cardiac pulmonary or other major medical illnesses Patients may not be allergic to eggs or hypersensitivity to any agents used in this trial must not require concomitant therapy with steroids
Design
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine and then will be treated by the adoptive transfer of lymphocytes reactive with the gp100209-217 melanoma antigen immunization with intravenous fowlpox virus rF-gp100P209 and the administration of high dose or low dose IL-2 Approximately 28 days after the cell infusion patients receiving high dose IL-2 will receive a second intravenous fowlpox virus rf-gp100P209 followed by administration of high dose IL-2 A complete evaluation of evaluable lesions will be conducted 6-8 weeks after cell infusion Patients receiving low dose IL-2 will receive a second intravenous fowlpox virus rf-gp100P209 after the 6 weeks of injections and one week of rest followed by repeat administration of the six week cycle of low dose IL-2 A complete evaluation of evaluable lesions will be conducted 3 weeks after the last dose of low dose IL-2 For each of the two cohorts a small optimal Phase II design will be used and will target 15 p1015 as a goal for complete response as opposed essentially zero probability normally associated with patients who relapse after high dose IL-2 alone p0002 will be used Initially 16 patients will be enrolled and evaluated in each cohort if at least 1 of the first 16 patients has a complete response then accrual to 29 patients will take place It is expected that it will require 2-3 years to accrue all 58 patients to this study
Recent clinical studies in the Surgery Branch have demonstrated clinical responses in patients undergoing adoptive transfer of autologous tumor reactive lymphocytes following a non-myeloablative immunosuppressive chemotherapy regimen Additional studies in the Surgery Branch using immunization with recombinant fowlpox virus after cell transfer in the immunosuppressed host have provided strong evidence to suggest that the adoptive transfer of lymphocytes in our clinical protocols in patients with melanoma will be substantially improved by the simultaneous administration of recombinant fowlpox virus
Objectives
The primary objective will be to determine whether gp100 reactive lymphocytes infused in conjunction with immunization with rf-gp100P209 and administration of high dose or low dose IL-2 may result in complete clinical tumor regression in patients with metastatic melanoma receiving a nonmyeloablative but lymphoid depleting preparative regimen Secondary objectives will be to determine the survival in patients of infused cells following this regimen and to determine the safety of this regimen
Eligibility
Patients who are HLA-A201 must be greater than or equal to 16 years of age and have measurable metastatic melanoma that is refractory to standard therapy Safety laboratory values must be within defined parameters More than four weeks must have elapsed since any prior systemic therapy Patients must be eligible to receive IL-2 and may not have cardiac pulmonary or other major medical illnesses Patients may not be allergic to eggs or hypersensitivity to any agents used in this trial must not require concomitant therapy with steroids
Design
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine and then will be treated by the adoptive transfer of lymphocytes reactive with the gp100209-217 melanoma antigen immunization with intravenous fowlpox virus rF-gp100P209 and the administration of high dose or low dose IL-2 Approximately 28 days after the cell infusion patients receiving high dose IL-2 will receive a second intravenous fowlpox virus rf-gp100P209 followed by administration of high dose IL-2 A complete evaluation of evaluable lesions will be conducted 6-8 weeks after cell infusion Patients receiving low dose IL-2 will receive a second intravenous fowlpox virus rf-gp100P209 after the 6 weeks of injections and one week of rest followed by repeat administration of the six week cycle of low dose IL-2 A complete evaluation of evaluable lesions will be conducted 3 weeks after the last dose of low dose IL-2 For each of the two cohorts a small optimal Phase II design will be used and will target 15 p1015 as a goal for complete response as opposed essentially zero probability normally associated with patients who relapse after high dose IL-2 alone p0002 will be used Initially 16 patients will be enrolled and evaluated in each cohort if at least 1 of the first 16 patients has a complete response then accrual to 29 patients will take place It is expected that it will require 2-3 years to accrue all 58 patients to this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-C-0152 | None | None | None |