Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001623
Status:
COMPLETED
Last Update Posted:
2019-12-12
First Post:
1999-11-03
Brief Title:
Bone Marrow Transplant Studies for Safe and Effective Treatment of Leukemia
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
HLA-Matched Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T Cell Add-Back for Hematological Malignancies
Status:
COMPLETED
Status Verified Date:
2017-08-03
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:
Bone marrow transplants BMT are one of the accepted therapies used to treat leukemia However BMT have risks of complications One potentially life-threatening complication is known as graft-versus-host disease GVHD
The GVHD is a reaction caused by an incompatibility between donor cells and recipient cells Antigens found on the recipient s cells are recognized by the donor s transplanted white blood cell lymphocytes These lymphocytes begin attacking the recipient s cells and tissues and may lead to death
One of the most effective ways to prevent this reaction is to remove the lymphocytes from the transplanted marrow Unfortunately without lymphocytes the recipient s immune system will be lowered and may result in a relapse of leukemia or an infection
Researchers have shown they can perform effective BMT by removing the lymphocytes prior to the transplant and then later adding the lymphocytes back This technique can reduce the potential for GVHD and preserve the graft-versus-leukemia GVL effect of the transplant
In this study researchers plan to use peripheral blood with lymphocytes removed rather than bone marrow In order to increase the number of progenitor cells the cells responsible for correcting the leukemia donors will receive doses of G-CSF prior to the transplant G-CSF granulocyte colony stimulating factor is a growth factor that increases the production of progenitor cells in the donor s blood stream
The study will be broken into two parts The first part of the study will attempt to determine if peripheral blood with lymphocytes removed can prevent GVHD while preserving the GVL effect of the transplant
In the second part of the study patients that received the transplant will have the lymphocytes added-back on two separate occasions in order reduce the chances of relapse and infection
The study is designed to treat up to 55 patients ages 10 to 60 years and follow their progress for 5 years
The GVHD is a reaction caused by an incompatibility between donor cells and recipient cells Antigens found on the recipient s cells are recognized by the donor s transplanted white blood cell lymphocytes These lymphocytes begin attacking the recipient s cells and tissues and may lead to death
One of the most effective ways to prevent this reaction is to remove the lymphocytes from the transplanted marrow Unfortunately without lymphocytes the recipient s immune system will be lowered and may result in a relapse of leukemia or an infection
Researchers have shown they can perform effective BMT by removing the lymphocytes prior to the transplant and then later adding the lymphocytes back This technique can reduce the potential for GVHD and preserve the graft-versus-leukemia GVL effect of the transplant
In this study researchers plan to use peripheral blood with lymphocytes removed rather than bone marrow In order to increase the number of progenitor cells the cells responsible for correcting the leukemia donors will receive doses of G-CSF prior to the transplant G-CSF granulocyte colony stimulating factor is a growth factor that increases the production of progenitor cells in the donor s blood stream
The study will be broken into two parts The first part of the study will attempt to determine if peripheral blood with lymphocytes removed can prevent GVHD while preserving the GVL effect of the transplant
In the second part of the study patients that received the transplant will have the lymphocytes added-back on two separate occasions in order reduce the chances of relapse and infection
The study is designed to treat up to 55 patients ages 10 to 60 years and follow their progress for 5 years
Detailed Description:
One of the most effective ways of preventing lethal graft-versus-host disease GVHD after allogeneic bone marrow transplantation BMT for leukemia is to remove T-lymphocytes from the transplanted marrow The reduced early mortality from T cell depletion is however offset by an increased risk of leukemic relapse and infection We have shown that bone marrow transplants for leukemia depleted of T cells by elutriation and followed by delayed add-back of donor T cells reduces GVHD while preserving an immune response to the hematologic malignancy the so-called graft-versus-leukemia GVL or graft-versus-myeloma effect The study highlighted a possible benefit of large doses of marrow progenitor cells on transplant outcome GVHD was reduced but not prevented by T cell depletion of the marrow The first objective of our BMT studies is to prevent GVHD from the transplant while conserving GVL reactivity This is a prerequisite to our second objective of determining the risk of GVHD and the benefit from GVL from add-back of donor lymphocytes These studies will provide the basis for a planned trial adding back donor lymphocytes selected in vitro to confer immunity against infectious agents and residual leukemia without causing GVHD
In this study we will evaluate the use of T cell depleted peripheral blood progenitor cells PBPC instead of bone marrow to optimize the stem cell and lymphocyte dose Donors will be given G-CSF and their mobilized PBPC harvested by leukapheresis To minimize acute GVHD the transplant will be T cell depleted using a new technique developed in normal volunteers which improves T cell depletion and reduces stem cell loss protocol 96-H-0049 The study has two phases The first phase evaluates engraftment and GVHD following T cell depleted PBPC transplants Stopping rules will be used to make modifications to the protocol in the event of graft failure Cyclosporine will be withdrawn from the protocol if the incidence of acute GVHD is low or absent In the second phase patients will receive add-back of donor lymphocytes on day 45 and day 100 post transplant to prevent relapse and confer donor-immune function The risk of acute GVHD following this procedure will be determined It is planned to treat up to 55 patients aged between 10 and 60 years The end points of the study are graft take acute and chronic GVHD leukemic relapse transplant-related and all causes of mortality cytomegalovirus reactivation and leukemia-free survival Patients will be followed for 5 years
In this study we will evaluate the use of T cell depleted peripheral blood progenitor cells PBPC instead of bone marrow to optimize the stem cell and lymphocyte dose Donors will be given G-CSF and their mobilized PBPC harvested by leukapheresis To minimize acute GVHD the transplant will be T cell depleted using a new technique developed in normal volunteers which improves T cell depletion and reduces stem cell loss protocol 96-H-0049 The study has two phases The first phase evaluates engraftment and GVHD following T cell depleted PBPC transplants Stopping rules will be used to make modifications to the protocol in the event of graft failure Cyclosporine will be withdrawn from the protocol if the incidence of acute GVHD is low or absent In the second phase patients will receive add-back of donor lymphocytes on day 45 and day 100 post transplant to prevent relapse and confer donor-immune function The risk of acute GVHD following this procedure will be determined It is planned to treat up to 55 patients aged between 10 and 60 years The end points of the study are graft take acute and chronic GVHD leukemic relapse transplant-related and all causes of mortality cytomegalovirus reactivation and leukemia-free survival Patients will be followed for 5 years
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 |
|---|---|---|---|
| 97-H-0099 | None | None | None |