Ignite Creation Date:
2024-05-05 @ 4:49 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00314106
Status:
COMPLETED
Last Update Posted:
2012-10-18
First Post:
2006-04-11
Brief Title:
Chemotherapy Irradiation Cell Infusions and Interleukin-2 to Treat Metastatic Melanoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase II Study Using a Myeloablative Lymphocyte Depleting Regimen of Chemotherapy and Intensive Total Body Irradiation Followed by Infusion of Tumor Reactive Lymphocytes and Reconstitution With CD34 Stem Cells in Metastatic Melanoma
Status:
COMPLETED
Status Verified Date:
2012-09
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:
Background
In a study in humans with melanoma patients given total body irradiation to suppress the immune system in conjunction with chemotherapy showed a significant clinical response
In previous studies about one-half of patients given tumor-fighting cells cells created from the patients tumor cells and grown in the laboratory showed some anti-tumor response
Objective To determine whether tumor-fighting cells taken from a melanoma tumor and grown in the lab can more effectively at fight melanoma when the patients immune system is suppressed and cannot attack them
Eligibility Patients 18 years of age or older with metastatic melanoma who have tumor reactive cells available
Design
-Patients are assigned to one of two groups - those having received prior therapy with Interleukin-2 IL-2 and those who have not
After five days of injections of filgrastim a medicine to stimulated the growth of white blood cells patients undergo apheresis or bone marrow harvesting or both to collect stem cells for later re-infusion For apheresis whole blood is collected through a needle in an arm vein and circulated through a cell-separating machine where the stem cells are extracted The rest of the blood is returned through the same needle or a needle in the other arm Bone marrow harvesting is done under general anesthesia Stem cells are collected through a large needle inserted into the hipbone-Patients immune system cells and bone marrow function are eliminated with chemotherapy 7 days and total body irradiation 3 days so the patients immune system cells will not fight the tumor-fighting cells they are given in treatment
1 to 3 days after total body irradiation patients receive the tumor-fighting cells by intravenous IV infusion After the cells are infused they receive interleukin-2 IL-2 infusions every 8 hours for 5 days
2 days after infusion of the tumor-fighting cells patients receive the stem cells collected earlier by apheresis
Patients are evaluated 4 to 6 weeks after cell infusion to look for tumor response to treatment Patients whose tumor has not grown return to the National Institutes of Health NIH every 1 to 3 months for blood tests scans and x-rays
In a study in humans with melanoma patients given total body irradiation to suppress the immune system in conjunction with chemotherapy showed a significant clinical response
In previous studies about one-half of patients given tumor-fighting cells cells created from the patients tumor cells and grown in the laboratory showed some anti-tumor response
Objective To determine whether tumor-fighting cells taken from a melanoma tumor and grown in the lab can more effectively at fight melanoma when the patients immune system is suppressed and cannot attack them
Eligibility Patients 18 years of age or older with metastatic melanoma who have tumor reactive cells available
Design
-Patients are assigned to one of two groups - those having received prior therapy with Interleukin-2 IL-2 and those who have not
After five days of injections of filgrastim a medicine to stimulated the growth of white blood cells patients undergo apheresis or bone marrow harvesting or both to collect stem cells for later re-infusion For apheresis whole blood is collected through a needle in an arm vein and circulated through a cell-separating machine where the stem cells are extracted The rest of the blood is returned through the same needle or a needle in the other arm Bone marrow harvesting is done under general anesthesia Stem cells are collected through a large needle inserted into the hipbone-Patients immune system cells and bone marrow function are eliminated with chemotherapy 7 days and total body irradiation 3 days so the patients immune system cells will not fight the tumor-fighting cells they are given in treatment
1 to 3 days after total body irradiation patients receive the tumor-fighting cells by intravenous IV infusion After the cells are infused they receive interleukin-2 IL-2 infusions every 8 hours for 5 days
2 days after infusion of the tumor-fighting cells patients receive the stem cells collected earlier by apheresis
Patients are evaluated 4 to 6 weeks after cell infusion to look for tumor response to treatment Patients whose tumor has not grown return to the National Institutes of Health NIH every 1 to 3 months for blood tests scans and x-rays
Detailed Description:
Background
The use of immunosuppression prior to adoptive transfer of lymphocytes from tumor bearing mice was based on a variety of murine models demonstrating improved therapeutic effectiveness of the adoptive transfer of lymphocytes following immunosuppression of the host
Because the degree of immunosuppression has been highly correlated with the ability to eliminate large tumors in murine models we have been conducting a clinical trial 04-C-0288 in which 200cGy of total body irradiation is used in conjunction with the same cyclophosphamide and fludarabine regimen used in our prior adoptive cell therapy trials which have demonstrated significant clinical responses
We have measured T-regulatory cells in patients participating in 04-C-0288 and have demonstrated that despite the addition of 200cGy total body irradiation TBI T-regulatory cells promptly reconstituted in the host Complete clinical responses have not been significantly improved over other adoptive cell therapy regimens
Thus in this trial we would like to more adequately test our hypothesis that more intensive lymphodepletion will increase complete responses and persistence of the transferred cells
Objective
To determine whether tumor reactive lymphocytes infused in conjunction with the administration of high-dose IL-2 in patients who have received prior therapy with IL-2 and those who have not may result in complete clinical tumor regression in patients with metastatic melanoma receiving a myeloablative lymphoid depleting preparative regimen
To evaluate the safety of the treatment in patients receiving the myeloablative conditioning regimen cell transfer and IL-2
To determine the survival in patients of infused cells following the administration of the myeloablative regimen using analysis of the sequence of the variable region of the T cell receptor or flow cytometry FACS
Eligibility
Patients who are greater than or equal to 18 years of age who have tumor reactive cells available with metastatic melanoma and are physically able to tolerate high-dose IL-2
Design
Patients will be assigned to one of two cohorts those having received prior therapy with IL-2 and those who have not
Patients will receive a myeloablative lymphocyte depleting preparative regimen consisting of cyclophosphamide 60 mgkgday x 2 days IV fludarabine 25mgm2day IV X 5 days and 1200 cGy total body irradiation TBI
Patients will receive intravenous adoptive transfer of tumor reactive lymphocytes minimum 3 X 10 9 and up to a maximum of 3 X 1011 lymphocytes followed by high-dose intravenous IV IL-2 720000 IUkgdose every 8 hours for up to 15 doses
On day 1 of patients will receive intravenous administration of cryopreserved autologous CD34 cells
A complete evaluation of evaluable lesions will be conducted 4-6 weeks after cell infusion Patients will be enrolled into two strata using a phase II optimal design to rule out a modest CR rate of 24 with 33-54 patients enrolled in each strata
The use of immunosuppression prior to adoptive transfer of lymphocytes from tumor bearing mice was based on a variety of murine models demonstrating improved therapeutic effectiveness of the adoptive transfer of lymphocytes following immunosuppression of the host
Because the degree of immunosuppression has been highly correlated with the ability to eliminate large tumors in murine models we have been conducting a clinical trial 04-C-0288 in which 200cGy of total body irradiation is used in conjunction with the same cyclophosphamide and fludarabine regimen used in our prior adoptive cell therapy trials which have demonstrated significant clinical responses
We have measured T-regulatory cells in patients participating in 04-C-0288 and have demonstrated that despite the addition of 200cGy total body irradiation TBI T-regulatory cells promptly reconstituted in the host Complete clinical responses have not been significantly improved over other adoptive cell therapy regimens
Thus in this trial we would like to more adequately test our hypothesis that more intensive lymphodepletion will increase complete responses and persistence of the transferred cells
Objective
To determine whether tumor reactive lymphocytes infused in conjunction with the administration of high-dose IL-2 in patients who have received prior therapy with IL-2 and those who have not may result in complete clinical tumor regression in patients with metastatic melanoma receiving a myeloablative lymphoid depleting preparative regimen
To evaluate the safety of the treatment in patients receiving the myeloablative conditioning regimen cell transfer and IL-2
To determine the survival in patients of infused cells following the administration of the myeloablative regimen using analysis of the sequence of the variable region of the T cell receptor or flow cytometry FACS
Eligibility
Patients who are greater than or equal to 18 years of age who have tumor reactive cells available with metastatic melanoma and are physically able to tolerate high-dose IL-2
Design
Patients will be assigned to one of two cohorts those having received prior therapy with IL-2 and those who have not
Patients will receive a myeloablative lymphocyte depleting preparative regimen consisting of cyclophosphamide 60 mgkgday x 2 days IV fludarabine 25mgm2day IV X 5 days and 1200 cGy total body irradiation TBI
Patients will receive intravenous adoptive transfer of tumor reactive lymphocytes minimum 3 X 10 9 and up to a maximum of 3 X 1011 lymphocytes followed by high-dose intravenous IV IL-2 720000 IUkgdose every 8 hours for up to 15 doses
On day 1 of patients will receive intravenous administration of cryopreserved autologous CD34 cells
A complete evaluation of evaluable lesions will be conducted 4-6 weeks after cell infusion Patients will be enrolled into two strata using a phase II optimal design to rule out a modest CR rate of 24 with 33-54 patients enrolled in each strata
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 |
|---|---|---|---|
| 06-C-0136 | None | None | None |