Ignite Creation Date:
2024-05-05 @ 4:49 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00328861
Status:
COMPLETED
Last Update Posted:
2012-11-04
First Post:
2006-05-20
Brief Title:
Natural Killer Cells Plus IL-2 Following Chemotherapy to Treat Advanced Melanoma or Kidney Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase II Study in Metastatic Melanoma or Kidney Cancer Using Autologous Natural Killer Cells Plus Aldesleukin IL-2 Following a Lymphodepleting Chemotherapy
Status:
COMPLETED
Status Verified Date:
2012-10
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
Natural killer NK cells are large lymphocytes a type of white blood cell that are important in the immune response to cancer
IL-2 Aldesleukin is a substance the body makes that controls the growth and function of many types of cells The Food and Drug Administration has approved IL-3 for treating metastatic melanoma and kidney cancer Metastatic disease is cancer that has spread beyond the primary site
Objectives To determine the safety and effectiveness of treating metastatic melanoma and kidney cancer with laboratory-treated NK cells and IL-2
Eligibility Patients 18 years of age or older with metastatic melanoma or kidney cancer who have previously been treated with high-dose IL-2
Design
Leukapheresis Patients under leukapheresis to obtain NK cells for the treatment regimen Blood is collected through a needle in an arm vein and directed through a cell separator machine where white blood cells are extracted The rest of the blood is returned to the patient through a needle in the other arm NK cells are removed from the white blood cells and treated for re-infusion into the patient
Chemotherapy Starting 8 days before infusion of the treated NK cells patients receive intravenous IV through a vein infusions of cyclophosphamide and fludarabine to suppress the immune system
NK cell infusion Patients receive a 30-minute IV infusion of NK cells 2 days after the last dose of chemotherapy
IL-2 therapy Within 24 hours of the NK cell infusion patients receive high-dose IL-2 as a 15-minute IV infusion every 8 hours for up to 5 days A second cycle of IL-2 is given about 14 days after the first
Blood tests and biopsy Patients have frequent blood tests during the treatment period and may be asked to undergo a biopsy surgical removal of a small piece of tumor or lymph node at the end of treatment to look at the effects of the treatment on the tumor immune cells
Follow-up evaluation Patients are evaluated 4-6 weeks after completing treatment They have a physical examination scans of tumor sites blood tests and blood sampling or leukapheresis to examine the response to treatment Patients who improve with treatment return for evaluations every month Those whose tumor grows again after originally shrinking may receive one additional treatment course
Natural killer NK cells are large lymphocytes a type of white blood cell that are important in the immune response to cancer
IL-2 Aldesleukin is a substance the body makes that controls the growth and function of many types of cells The Food and Drug Administration has approved IL-3 for treating metastatic melanoma and kidney cancer Metastatic disease is cancer that has spread beyond the primary site
Objectives To determine the safety and effectiveness of treating metastatic melanoma and kidney cancer with laboratory-treated NK cells and IL-2
Eligibility Patients 18 years of age or older with metastatic melanoma or kidney cancer who have previously been treated with high-dose IL-2
Design
Leukapheresis Patients under leukapheresis to obtain NK cells for the treatment regimen Blood is collected through a needle in an arm vein and directed through a cell separator machine where white blood cells are extracted The rest of the blood is returned to the patient through a needle in the other arm NK cells are removed from the white blood cells and treated for re-infusion into the patient
Chemotherapy Starting 8 days before infusion of the treated NK cells patients receive intravenous IV through a vein infusions of cyclophosphamide and fludarabine to suppress the immune system
NK cell infusion Patients receive a 30-minute IV infusion of NK cells 2 days after the last dose of chemotherapy
IL-2 therapy Within 24 hours of the NK cell infusion patients receive high-dose IL-2 as a 15-minute IV infusion every 8 hours for up to 5 days A second cycle of IL-2 is given about 14 days after the first
Blood tests and biopsy Patients have frequent blood tests during the treatment period and may be asked to undergo a biopsy surgical removal of a small piece of tumor or lymph node at the end of treatment to look at the effects of the treatment on the tumor immune cells
Follow-up evaluation Patients are evaluated 4-6 weeks after completing treatment They have a physical examination scans of tumor sites blood tests and blood sampling or leukapheresis to examine the response to treatment Patients who improve with treatment return for evaluations every month Those whose tumor grows again after originally shrinking may receive one additional treatment course
Detailed Description:
Background
Natural killer NK cells are large granular lymphocytes that are critical effector cells in the early innate immune response to pathogens and cancer
Previous and current clinical investigations have clearly demonstrated that T lymphocytes can mediate the regression of metastatic melanoma However not all patients with cancer are eligible for this type of immunotherapy either because resectable tumor is not available the TIL do not expand sufficiently or the tumor infiltrating lymphocytes TIL that do proliferate do not exhibit sufficient tumor specific reactivity
We have recently developed techniques for the in vitro isolation and expansion of anti-tumor NK cells to levels suitable for the treatment of cancer patients and are proposing in this protocol to evaluate therapy using these NK cells
In Surgery Branch pre-clinical experiments we evaluated lysis of fresh melanoma cell digests melanoma cell lines renal cell carcinoma RCC lines and normal peripheral blood mononuclear cells PBMCs by NK cells from several patients and demonstrated that NK cells could lyse some fresh melanoma digests as well as melanoma cell lines and renal cell cancer RCC lines while sparing normal allogeneic and autologous PBMCs
Objectives
Determine the ability of the administration of autologous natural killer NK cells plus aldesleukin IL-2 following a non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma or kidney cancer
Determine the rate of repopulation of the natural killer cells in treated patients
Determine the toxicity of this treatment regimen
Eligibility
Patients 18 years of age or older with metastatic melanoma or metastatic kidney cancer who have previously received high dose IL-2 with an Eastern Cooperative Oncology Group ECOG of 0 or 1
Patients may not have any active systemic infections coagulations disorders major medical illnesses of the cardiovascular respiratory or immune systems or any form of autoimmune disease or immunodeficiency
Patients must be eligible to receive high-dose IL-2
Design
Patients will undergo apheresis on 03-C-0277 Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols to obtain cells for generation of autologous natural killer cells
All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide 60 mgkgday IV on days -8 and -7 and fludarabine 25 mgm2day IV on days -6 through -2
On day 0 patients will receive the infusion of autologous natural killer lymphocytes and then begin the first cycle of high-dose IL-2 720000 IUkg IV every 8 hours for up to 15 doses A second cycle of IL-2 will be administered approximately 14 days later
Clinical and Immunologic response will be evaluated about 4 to 6 weeks
after the second cycle of IL-2
-Using a small optimal Phase II design two cohorts of patients initially 16 in each cohort will be enrolled and if at least one of the first 16 patients has a clinical response partial response PR or complete response CR accrual will continue to 29 patients targeting a 15 goal for objective response
Natural killer NK cells are large granular lymphocytes that are critical effector cells in the early innate immune response to pathogens and cancer
Previous and current clinical investigations have clearly demonstrated that T lymphocytes can mediate the regression of metastatic melanoma However not all patients with cancer are eligible for this type of immunotherapy either because resectable tumor is not available the TIL do not expand sufficiently or the tumor infiltrating lymphocytes TIL that do proliferate do not exhibit sufficient tumor specific reactivity
We have recently developed techniques for the in vitro isolation and expansion of anti-tumor NK cells to levels suitable for the treatment of cancer patients and are proposing in this protocol to evaluate therapy using these NK cells
In Surgery Branch pre-clinical experiments we evaluated lysis of fresh melanoma cell digests melanoma cell lines renal cell carcinoma RCC lines and normal peripheral blood mononuclear cells PBMCs by NK cells from several patients and demonstrated that NK cells could lyse some fresh melanoma digests as well as melanoma cell lines and renal cell cancer RCC lines while sparing normal allogeneic and autologous PBMCs
Objectives
Determine the ability of the administration of autologous natural killer NK cells plus aldesleukin IL-2 following a non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma or kidney cancer
Determine the rate of repopulation of the natural killer cells in treated patients
Determine the toxicity of this treatment regimen
Eligibility
Patients 18 years of age or older with metastatic melanoma or metastatic kidney cancer who have previously received high dose IL-2 with an Eastern Cooperative Oncology Group ECOG of 0 or 1
Patients may not have any active systemic infections coagulations disorders major medical illnesses of the cardiovascular respiratory or immune systems or any form of autoimmune disease or immunodeficiency
Patients must be eligible to receive high-dose IL-2
Design
Patients will undergo apheresis on 03-C-0277 Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols to obtain cells for generation of autologous natural killer cells
All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide 60 mgkgday IV on days -8 and -7 and fludarabine 25 mgm2day IV on days -6 through -2
On day 0 patients will receive the infusion of autologous natural killer lymphocytes and then begin the first cycle of high-dose IL-2 720000 IUkg IV every 8 hours for up to 15 doses A second cycle of IL-2 will be administered approximately 14 days later
Clinical and Immunologic response will be evaluated about 4 to 6 weeks
after the second cycle of IL-2
-Using a small optimal Phase II design two cohorts of patients initially 16 in each cohort will be enrolled and if at least one of the first 16 patients has a clinical response partial response PR or complete response CR accrual will continue to 29 patients targeting a 15 goal for objective response
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-0169 | None | None | None |