Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001144
Status:
COMPLETED
Last Update Posted:
2008-10-07
First Post:
1999-11-03
Brief Title:
Modified Bone Marrow Stem Cell Transplantation for Chronic Myelogenous Leukemia
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Non-Myeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Chronic Phase CML
Status:
COMPLETED
Status Verified Date:
2002-10
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:
This study will investigate the safety and effectiveness of a new stem cell transplant procedure for treating chronic myelogenous leukemia CML
Transplantation of donated stem cells cells produced by the bone marrow that mature into the different blood components-white cells red cells and platelets is a very effective treatment for CML However despite its success in a large number of patients there is still a significant risk of death from the procedure In addition it results in sterility and leaves patients at increased risk for other cancers and for eye cataracts These complications result from the intensive chemotherapy and radiation patients receive before the transplant to rid the body of cancer cells In this study radiation will not be used and chemotherapy drugs will be given in lower doses to try to reduce the dangers of the procedure
Patients with CML will be tested for matching with a donor family member and will undergo a medical history physical examination and several tests eg breathing tests X-rays and others to determine eligibility for the study Participants will then undergo apheresis to collect lymphocytes white blood cells important in the immune system In apheresis whole blood is drawn through a needle in the arm similar to donating a unit of blood The required component-in this case lymphocytes-are separated and removed and the rest of the blood is returned through a needle in the other arm
Each day starting five days before the transplant the donor will be given an injection of G-CSF a drug that releases stem cells from the bone marrow into the blood stream The cells will be collected after the fifth injection and again after a sixth injection the following day Meanwhile patients will be given cyclophosphamide and fludarabine and perhaps anti-thymocyte globulin to prevent rejection of the donated cells
On the day of the transplant patients will be given cyclosporin to prevent graft-versus-host-disease a disease in which the donor cells react against the patients cells They may also be given lymphocytes after the transplant to boost the immune system and destroy leukemia cells After 30 60 and 100 days bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin If less than 100 percent are of donor origin more lymphocytes will be transfused Patients will have physical examinations and blood tests at least weekly for 3 months and then periodically for 5 years
Transplantation of donated stem cells cells produced by the bone marrow that mature into the different blood components-white cells red cells and platelets is a very effective treatment for CML However despite its success in a large number of patients there is still a significant risk of death from the procedure In addition it results in sterility and leaves patients at increased risk for other cancers and for eye cataracts These complications result from the intensive chemotherapy and radiation patients receive before the transplant to rid the body of cancer cells In this study radiation will not be used and chemotherapy drugs will be given in lower doses to try to reduce the dangers of the procedure
Patients with CML will be tested for matching with a donor family member and will undergo a medical history physical examination and several tests eg breathing tests X-rays and others to determine eligibility for the study Participants will then undergo apheresis to collect lymphocytes white blood cells important in the immune system In apheresis whole blood is drawn through a needle in the arm similar to donating a unit of blood The required component-in this case lymphocytes-are separated and removed and the rest of the blood is returned through a needle in the other arm
Each day starting five days before the transplant the donor will be given an injection of G-CSF a drug that releases stem cells from the bone marrow into the blood stream The cells will be collected after the fifth injection and again after a sixth injection the following day Meanwhile patients will be given cyclophosphamide and fludarabine and perhaps anti-thymocyte globulin to prevent rejection of the donated cells
On the day of the transplant patients will be given cyclosporin to prevent graft-versus-host-disease a disease in which the donor cells react against the patients cells They may also be given lymphocytes after the transplant to boost the immune system and destroy leukemia cells After 30 60 and 100 days bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin If less than 100 percent are of donor origin more lymphocytes will be transfused Patients will have physical examinations and blood tests at least weekly for 3 months and then periodically for 5 years
Detailed Description:
CML is a disease which progresses to blast crisis within five years of onset despite medical intervention Allogeneic transplantation has provided a definitive cure for a large number of patients The International Bone Marrow transplant registry reports a 67 three-year disease free survival for CML patients receiving a matched sibling transplant However there remains a 17-20 treatment-related mortality and significant long-term complications Myeloablative regimens with total body irradiation TBI are associated with certain sterility along with a significant incidence of cataracts and second malignancies Efforts to ameliorate this toxicity have led to the development of regimens lacking total body irradiation Although the follow-up period for patients receiving these regimens has not been long enough to answer the question of long-term toxicity it appears that the response rate and the disease free survival are comparable to regimens containing TBI In addition transplantation experience with aplastic anemia where TBI is not part of the regimen indicates that treatment related mortality along with the risk of long-term sequela are significantly decreased
Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being investigated in phase III trials assessing engraftment efficacy and toxicity at a number of transplant centers Preliminary data including our own experience with 30 patients undergoing this type of procedure has shown a high rate of complete donor engraftment with a low toxicity profile Two recent studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant-related complications and mortality
In this protocol we investigate non-myeloablative allogeneic PBSC transplantation in patients with CML The patient group under study would include all patients with chronic phase CML having an HLA-identical sibling In this protocol eligible patients would be treated with an allogeneic peripheral blood stem cell transplant from an HLA identical or single HLA antigen-mismatched family donor using an intensive immunosuppressive regimen without myeloablation mini-transplant in an attempt to decrease the transplant related toxicities while preserving the anti-malignancy andor anti-host marrow effect of the graft The low intensity non-myeloablative conditioning regimen should provide adequate immunosuppression to allow stem cell and lymphocyte engraftment T-cell replete donor-derived granulocyte colony stimulating factor G-CSF-mobilized peripheral blood stem cells PBSC will be used to establish hematopoietic and lymphoid reconstitution We will add back lymphocytes in patients with less than 100 donor T-cell chimerism in an attempt to prevent graft rejection and enhance a graft-versus-malignancy effect
The primary endpoint of this study is transplant related mortality 1 year survival Other end points include engraftment degree of donor-host chimerism incidence of acute and chronic graft versus host disease GVHD transplant related morbidity as well as disease-free and overall survival
Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being investigated in phase III trials assessing engraftment efficacy and toxicity at a number of transplant centers Preliminary data including our own experience with 30 patients undergoing this type of procedure has shown a high rate of complete donor engraftment with a low toxicity profile Two recent studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant-related complications and mortality
In this protocol we investigate non-myeloablative allogeneic PBSC transplantation in patients with CML The patient group under study would include all patients with chronic phase CML having an HLA-identical sibling In this protocol eligible patients would be treated with an allogeneic peripheral blood stem cell transplant from an HLA identical or single HLA antigen-mismatched family donor using an intensive immunosuppressive regimen without myeloablation mini-transplant in an attempt to decrease the transplant related toxicities while preserving the anti-malignancy andor anti-host marrow effect of the graft The low intensity non-myeloablative conditioning regimen should provide adequate immunosuppression to allow stem cell and lymphocyte engraftment T-cell replete donor-derived granulocyte colony stimulating factor G-CSF-mobilized peripheral blood stem cells PBSC will be used to establish hematopoietic and lymphoid reconstitution We will add back lymphocytes in patients with less than 100 donor T-cell chimerism in an attempt to prevent graft rejection and enhance a graft-versus-malignancy effect
The primary endpoint of this study is transplant related mortality 1 year survival Other end points include engraftment degree of donor-host chimerism incidence of acute and chronic graft versus host disease GVHD transplant related morbidity as well as disease-free and overall survival
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 |
|---|---|---|---|
| 00-H-0001 | None | None | None |