Ignite Creation Date:
2024-05-05 @ 11:19 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000603
Status:
COMPLETED
Last Update Posted:
2016-04-14
First Post:
1999-10-27
Brief Title:
Cord Blood Stem Cell Transplantation Study COBLT
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2008-01
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:
To evaluate if HLA-mismatched unrelated-donor umbilical cord blood stem and progenitor cell units UCBU offered a clinically acceptable alternative to matched unrelated-donor allogeneic bone marrow for transplantation with 180-day disease free survival as the endpoint HLA typing was performed using DNA-base high resolution methods to determine HLA alleles Patients with true HLA 36 and 46 matches were evaluated In addition a separate study in adults addressed the problem of limited cell dose and engraftment failure The study was not planned as a randomized comparative clinical trial Instead it is a phase IIIII efficacy study
Detailed Description:
BACKGROUND
Bone marrow transplantation is an effective therapy for a variety of genetic and hematologic disorders Donated bone marrow which provides a source of stem and progenitor cells for bone marrow reconstitution is obtained either from related donors usually HLA-matched siblings or from HLA-matched unrelated donors Because of the limited availability of HLA-matched related donors HLA-matched unrelated donors are frequently the only alternative source of bone marrow for transplantation To provide matched volunteer bone marrow donors for unrelated recipients the National Marrow Donor Program NMDP was established in 1986 to develop a national Registry of HLA-typed individuals who agree to donate bone marrow if needed More than 3 million potential marrow donors are now enrolled A limitation of the registry approach is the time needed to identify a donor and complete the necessary clinical evaluation and laboratory testing for histocompatibility infectious diseases and general good health Moreover a certain proportion of potential donors change their minds or otherwise become unavailable between the time they enter the Registry and the time they are called as a preliminary match for a patient Another disadvantage is the marrow harvesting procedure which requires the normal donor to be hospitalized and given general anesthesia in an operating room Finally the NMDP Registry consists of potential donors that are primarily of European Caucasian ancestry Although great strides have been made in increasing the numbers of African-Americans Hispanics Asian-Americans and Native Americans it is still more difficult to find matches for these ethnic minorities than for Caucasian patients
Human umbilical cord blood is an alternative source of hematopoietic stem and progenitor cells capable of reconstituting the bone marrow of recipients with a variety of diseases Cord blood stem and progenitor cells from related donors have been successfully transplanted world-wide in children with genetic or hematologic diseases These results suggested that cord blood from unrelated HLA-matched donors also can be used for patients who need a transplant but dont have a related donor The existing problems in unrelated-donor bone marrow transplantation with donor recruitment bone marrow harvesting and matching for antigens peculiar to a particular ethnic group would be reduced if typed tested and frozen umbilical cord blood could be made easily and rapidly available Such a system which could complement or partially replace the present process has been shown to be feasible In an NHLBI-sponsored program investigators have collected and cryopreserved a bank of about 9000 human UCBUs In addition successful searches and matches including many 46 antigen matches have resulted in more than 900 unrelated-donor UCBU transplants to date Preliminary data from both these unrelated-donor and other related-donor cord blood transplants suggest that there is less GvHD than if the source of the graft were adult bone marrow The severity of GvHD also seems less even in highly mismatched recipients One important question is whether or not 36 HLA matched transplants in children will have acceptable 180-day disease free survival It also remains to be determined if the graft-vs-leukemia effect is also less or if unrelated-donor cord blood grafts are as durable as those from matched related-donors Most transplants conducted thus far have been in children Hence another important question is whether or not there are sufficient numbers of stem cells in cord blood to support transplantation to an unrelated adult
The initiative was proposed by the Division of Blood Diseases and Resources staff and approved by the February 1995 National Heart Lung and Blood Advisory Council The Requests for Proposals were released in June 1995 Contracts were awarded September 30 1997
DESIGN NARRATIVE
The study is multicenter with six Cord Blood Transplant Centers CBTCs two collecting and storage centers Cord Blood Banks -- CBBs and one Coordinating Center Each CBB used the same protocol for recruiting donors collecting processing testing storage retrieval from storage reprocessing from the frozen state and shipping Each participating CBTC used the same patient selection criteria preparative regimen for patients in the same class initial graft-versus-host disease GvHD prophylaxis indications for the use of cytokines definitions for events and complications and methods for evaluating immune reconstitution The main study evaluated the impact of HLA 36 and 46 matching on outcome The primary endpoint was 180-day disease free survival after UCBU transplantation Secondary endpoints included engraftment the frequency and severity of acute and chronic GvHD with stratification by degree of HLA match overall survival and immunologic reconstitution Data were collected on banked UCBUs to define unit quality by nucleated cell count and flow cytometry of surface markers to identify effects on patient outcome Recruitment ended December 31 2003 with the accrual of 326 subjects
Bone marrow transplantation is an effective therapy for a variety of genetic and hematologic disorders Donated bone marrow which provides a source of stem and progenitor cells for bone marrow reconstitution is obtained either from related donors usually HLA-matched siblings or from HLA-matched unrelated donors Because of the limited availability of HLA-matched related donors HLA-matched unrelated donors are frequently the only alternative source of bone marrow for transplantation To provide matched volunteer bone marrow donors for unrelated recipients the National Marrow Donor Program NMDP was established in 1986 to develop a national Registry of HLA-typed individuals who agree to donate bone marrow if needed More than 3 million potential marrow donors are now enrolled A limitation of the registry approach is the time needed to identify a donor and complete the necessary clinical evaluation and laboratory testing for histocompatibility infectious diseases and general good health Moreover a certain proportion of potential donors change their minds or otherwise become unavailable between the time they enter the Registry and the time they are called as a preliminary match for a patient Another disadvantage is the marrow harvesting procedure which requires the normal donor to be hospitalized and given general anesthesia in an operating room Finally the NMDP Registry consists of potential donors that are primarily of European Caucasian ancestry Although great strides have been made in increasing the numbers of African-Americans Hispanics Asian-Americans and Native Americans it is still more difficult to find matches for these ethnic minorities than for Caucasian patients
Human umbilical cord blood is an alternative source of hematopoietic stem and progenitor cells capable of reconstituting the bone marrow of recipients with a variety of diseases Cord blood stem and progenitor cells from related donors have been successfully transplanted world-wide in children with genetic or hematologic diseases These results suggested that cord blood from unrelated HLA-matched donors also can be used for patients who need a transplant but dont have a related donor The existing problems in unrelated-donor bone marrow transplantation with donor recruitment bone marrow harvesting and matching for antigens peculiar to a particular ethnic group would be reduced if typed tested and frozen umbilical cord blood could be made easily and rapidly available Such a system which could complement or partially replace the present process has been shown to be feasible In an NHLBI-sponsored program investigators have collected and cryopreserved a bank of about 9000 human UCBUs In addition successful searches and matches including many 46 antigen matches have resulted in more than 900 unrelated-donor UCBU transplants to date Preliminary data from both these unrelated-donor and other related-donor cord blood transplants suggest that there is less GvHD than if the source of the graft were adult bone marrow The severity of GvHD also seems less even in highly mismatched recipients One important question is whether or not 36 HLA matched transplants in children will have acceptable 180-day disease free survival It also remains to be determined if the graft-vs-leukemia effect is also less or if unrelated-donor cord blood grafts are as durable as those from matched related-donors Most transplants conducted thus far have been in children Hence another important question is whether or not there are sufficient numbers of stem cells in cord blood to support transplantation to an unrelated adult
The initiative was proposed by the Division of Blood Diseases and Resources staff and approved by the February 1995 National Heart Lung and Blood Advisory Council The Requests for Proposals were released in June 1995 Contracts were awarded September 30 1997
DESIGN NARRATIVE
The study is multicenter with six Cord Blood Transplant Centers CBTCs two collecting and storage centers Cord Blood Banks -- CBBs and one Coordinating Center Each CBB used the same protocol for recruiting donors collecting processing testing storage retrieval from storage reprocessing from the frozen state and shipping Each participating CBTC used the same patient selection criteria preparative regimen for patients in the same class initial graft-versus-host disease GvHD prophylaxis indications for the use of cytokines definitions for events and complications and methods for evaluating immune reconstitution The main study evaluated the impact of HLA 36 and 46 matching on outcome The primary endpoint was 180-day disease free survival after UCBU transplantation Secondary endpoints included engraftment the frequency and severity of acute and chronic GvHD with stratification by degree of HLA match overall survival and immunologic reconstitution Data were collected on banked UCBUs to define unit quality by nucleated cell count and flow cytometry of surface markers to identify effects on patient outcome Recruitment ended December 31 2003 with the accrual of 326 subjects
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: