Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00079625
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2004-03-09
Brief Title:
Stem Cell Transplant With Th2Tc2 Cells to Treat Advanced Breast Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Allogeneic Breast Protocol 2 Phase I Trial of T Cell Exchange With Th2Tc2 Cells for Allogeneic Stem Cell Transplantation After Reduced Intensity Conditioning for Metastatic Breast Cancer
Status:
COMPLETED
Status Verified Date:
2013-08-09
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:
This Phase 1 trial will investigate the safety of a modified stem cell transplant procedure for treating advanced breast cancer Patients with cancers can sometimes benefit greatly from transplants of stem cells cells produced by the bone marrow that mature into blood cells In addition to producing new bone marrow and restoring normal blood production and immunity the donated cells fight any residual tumor cells that might have remained in the body in what is called a graft-versus-tumor effect However severe problems or sometimes even death may follow these transplants as a result of the high-dose chemotherapy and radiation that accompany the procedure Also donated immune cells called lymphocytes or T cells sometimes attack healthy tissues in a reaction called graft-versus-host-disease GVHD damaging organs such as the liver intestines and skin This study will use the following strategies to try to reduce these risks
Induction chemotherapy to reduce patients immunity in an attempt to prevent rejection of the donated stem cells
Reduced-intensity conditioning chemotherapy that is easier for the body to tolerate and involves a shorter period of complete immune suppression
Removal of lymphocytes from the donor stem cells for transfusion in small quantities at monthly intervals following the stem cell transplant to reduce the risk of GVHD
Transplant of specific lymphocytes called Th2Tc2 cells that may increase the percentage of donor stem cells accepted by the patient without significantly increasing GVHD
Patients between 18 and 75 years of age with advanced stage IV breast cancer that does not respond to standard therapy may be eligible for this study Candidates are screened with a medical history physical and dental examinations x-ray studies and bone marrow biopsies to evaluate disease status blood and urine tests including a blood test for genetic match with the donor and lung and heart function tests
Participants have a central venous line large plastic tube placed into a major vein This tube stays in the body during the entire treatment period for infusing the donated stem cells and T lymphocytes giving medications including chemotherapy and other drugs antibiotics and blood transfusions and withdrawing blood samples Treatment starts with induction chemotherapy in which patients receive one or two cycles of the anti-cancer drugs fludarabine and cyclophosphamide One cycle consists of 4 days on drug therapy followed by a 17-day rest period G-CSF a drug that boosts white cell production is also given to reduce the risk of infection Several days before the transplant procedure patients begin conditioning chemotherapy with higher doses of cyclophosphamide and fludarabine Three days after the conditioning therapy is completed the stem cells are infused To help prevent both rejection of the donor stem cells and GVHD patients receive cyclosporine first by vein and later by mouth for several weeks after the transplant Infusions of donor lymphocytes begin about 6 weeks after the transplant to boost the immune system and enhance the graft-versus-tumor effect
Patients may leave the hospital when they are able to eat and drink have no fever or infection and have a normal or near-normal white cell count They return for follow-up visits twice a week for the first 100 days after the transplant then every 3 months then 6 months and then yearly for at least 5 years post-transplant The visits include a medical history physical examination and blood draws as well as disease staging with CT scans every month for the first 6 months
Induction chemotherapy to reduce patients immunity in an attempt to prevent rejection of the donated stem cells
Reduced-intensity conditioning chemotherapy that is easier for the body to tolerate and involves a shorter period of complete immune suppression
Removal of lymphocytes from the donor stem cells for transfusion in small quantities at monthly intervals following the stem cell transplant to reduce the risk of GVHD
Transplant of specific lymphocytes called Th2Tc2 cells that may increase the percentage of donor stem cells accepted by the patient without significantly increasing GVHD
Patients between 18 and 75 years of age with advanced stage IV breast cancer that does not respond to standard therapy may be eligible for this study Candidates are screened with a medical history physical and dental examinations x-ray studies and bone marrow biopsies to evaluate disease status blood and urine tests including a blood test for genetic match with the donor and lung and heart function tests
Participants have a central venous line large plastic tube placed into a major vein This tube stays in the body during the entire treatment period for infusing the donated stem cells and T lymphocytes giving medications including chemotherapy and other drugs antibiotics and blood transfusions and withdrawing blood samples Treatment starts with induction chemotherapy in which patients receive one or two cycles of the anti-cancer drugs fludarabine and cyclophosphamide One cycle consists of 4 days on drug therapy followed by a 17-day rest period G-CSF a drug that boosts white cell production is also given to reduce the risk of infection Several days before the transplant procedure patients begin conditioning chemotherapy with higher doses of cyclophosphamide and fludarabine Three days after the conditioning therapy is completed the stem cells are infused To help prevent both rejection of the donor stem cells and GVHD patients receive cyclosporine first by vein and later by mouth for several weeks after the transplant Infusions of donor lymphocytes begin about 6 weeks after the transplant to boost the immune system and enhance the graft-versus-tumor effect
Patients may leave the hospital when they are able to eat and drink have no fever or infection and have a normal or near-normal white cell count They return for follow-up visits twice a week for the first 100 days after the transplant then every 3 months then 6 months and then yearly for at least 5 years post-transplant The visits include a medical history physical examination and blood draws as well as disease staging with CT scans every month for the first 6 months
Detailed Description:
Background
In CC 00-C-0119 we were able to demonstrate that allogeneic T cells could mediate a clinically relevant graft-versus-tumor GVT effect against MBC after a reduced-intensity T cell depleted allogeneic hematopoietic stem cell transplant alloHSCT
Responses were observed after establishment of complete lymphoid chimerism which was frequently delayed and required the use of planned donor lymphocyte infusions DLI DLI were associated with a significant incidence of graft-versus-host disease GVHD
In murine models in vitro generated T cells of Th2Tc2 phenotype can facilitate engraftment of HLA disparate allografts with significantly reduced GVHD as compared to T cell replete allografts that have not been manipulated In addition Th2Tc2 cells provide an anti-tumor effect through the perforingranzyme pathway
Allogeneic Th2Tc2 cells may facilitate rapid allo-engraftment post-transplant with reduced GVHD In addition the perforin-mediated anti-tumor activity of Th2Tc2 cells should provide earlier benefit compared with T-cell depleted allografts
Objectives
-To determine the safety as defined by the incidence of acute graft-versus-host disease and feasibility of administering in vitro generated donor T cells of Th2Tc2 phenotype to augment a T cell depleted allograft T cell exchange after reduced-intensity conditioning
Eligibility
Patients with measurable metastatic breast cancer and an HLA matched sibling donor
Patients must have received treatment with a taxane an anthracycline a hormonal agent andor Herceptin if the tumor expresses the respective receptors and at least one treatment for metastatic disease that has not resulted in a complete response
Design
Donors will initially have lymphocytes collected to generate the Th2Tc2 product and then have blood stem cells collected following mobilization with filgrastim The stem cell product will be T-cell depleted and the T-cell dose will be adjusted to 1 x 105 CD3 cellskg
Patients will receive induction immune depleting chemotherapy with the goal of reducing circulating CD4 cell less than 50microliter prior to proceeding to alloHSCT
Patients will receive a reduced-intensity conditioning regimen consisting of fludarabine and cyclophosphamide This will be followed by infusion of the T cell depleted allograft which will be supplemented with Th2Tc2 cells ie T cell exchange
Cyclosporine will be discontinued after 40 days to permit a full GVT effect Patients may receive donor lymphocyte infusions at days 42 70 98 post-transplant to further potentiate a GVT effect
Patients will be enrolled in three cohorts with escalating Th2Tc2 cell doses 05 - 125 x 107 cellskg given in a phase-I manner
In CC 00-C-0119 we were able to demonstrate that allogeneic T cells could mediate a clinically relevant graft-versus-tumor GVT effect against MBC after a reduced-intensity T cell depleted allogeneic hematopoietic stem cell transplant alloHSCT
Responses were observed after establishment of complete lymphoid chimerism which was frequently delayed and required the use of planned donor lymphocyte infusions DLI DLI were associated with a significant incidence of graft-versus-host disease GVHD
In murine models in vitro generated T cells of Th2Tc2 phenotype can facilitate engraftment of HLA disparate allografts with significantly reduced GVHD as compared to T cell replete allografts that have not been manipulated In addition Th2Tc2 cells provide an anti-tumor effect through the perforingranzyme pathway
Allogeneic Th2Tc2 cells may facilitate rapid allo-engraftment post-transplant with reduced GVHD In addition the perforin-mediated anti-tumor activity of Th2Tc2 cells should provide earlier benefit compared with T-cell depleted allografts
Objectives
-To determine the safety as defined by the incidence of acute graft-versus-host disease and feasibility of administering in vitro generated donor T cells of Th2Tc2 phenotype to augment a T cell depleted allograft T cell exchange after reduced-intensity conditioning
Eligibility
Patients with measurable metastatic breast cancer and an HLA matched sibling donor
Patients must have received treatment with a taxane an anthracycline a hormonal agent andor Herceptin if the tumor expresses the respective receptors and at least one treatment for metastatic disease that has not resulted in a complete response
Design
Donors will initially have lymphocytes collected to generate the Th2Tc2 product and then have blood stem cells collected following mobilization with filgrastim The stem cell product will be T-cell depleted and the T-cell dose will be adjusted to 1 x 105 CD3 cellskg
Patients will receive induction immune depleting chemotherapy with the goal of reducing circulating CD4 cell less than 50microliter prior to proceeding to alloHSCT
Patients will receive a reduced-intensity conditioning regimen consisting of fludarabine and cyclophosphamide This will be followed by infusion of the T cell depleted allograft which will be supplemented with Th2Tc2 cells ie T cell exchange
Cyclosporine will be discontinued after 40 days to permit a full GVT effect Patients may receive donor lymphocyte infusions at days 42 70 98 post-transplant to further potentiate a GVT effect
Patients will be enrolled in three cohorts with escalating Th2Tc2 cell doses 05 - 125 x 107 cellskg given in a phase-I manner
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-0131 | None | None | None |