Ignite Creation Date:
2024-05-05 @ 7:07 PM
Last Modification Date:
2024-10-26 @ 9:43 AM
Study NCT ID:
NCT00604201
Status:
COMPLETED
Last Update Posted:
2022-01-05
First Post:
2008-01-08
Brief Title:
Stem Cell Transplant Using Peripheral and Cord Blood Stem Cells to Treat Severe Aplastic Anemia and Myelodysplastic Syndrome
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Co-Infusion of Umbilical Cord Blood and Haploidentical CD34 Cells Following Nonmyeloablative Conditioning as Treatment for Severe Aplastic Anemia and MDS Associated With Severe Neutropenia Refractory to Immunosuppressive Therapy
Status:
COMPLETED
Status Verified Date:
2021-12
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 evaluate the safety and effectiveness of treating patients with severe aplastic anemia SAA or myelodysplastic syndrome MDS with both peripheral blood stem cells from a family member and umbilical cord blood stem cells from an unrelated donor
Patients with SAA or MDS for whom other treatments have failed or are not available may be eligible for this study Candidates may not have a tissue-matched sibling or matched unrelated donor and must have a family member who is a partial tissue type match
Participants undergo the following tests and procedures
Insertion of a central intravenous IV line plastic tube into a large vein The tube is used for giving the donated stem cells and antibiotics and other medicines for transfusions of red blood cells and platelets and for collecting blood samples
Preparatory chemotherapy fludarabine cyclophosphamide and anti-thymocyte globulin and total body irradiation to suppress immunity and prevent rejection of the donated cells
Infusion of the donated stem cells and umbilical cord cells
Immune suppression with the drugs tacrolimus mycophenolate mofetil and prednisone to prevent rejection of the donated cells and to prevent graft-versus-host disease GVHD a complication of stem cell transplants in which the donors immune cells destroy the patients healthy tissues
The average hospital stay after stem cell transplantation is 3 to 4 weeks Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation Once the patient returns home his or her referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter Patient follow-up visits are scheduled at NIH at 1 2 3 4 and 5 years after transplantation to monitor for signs of disease or post-transplantation complications such as infection or GVHD After 5 years participants are offered the opportunity to enroll in NHLBIs long-term evaluation and follow-up care protocol
Patients with SAA or MDS for whom other treatments have failed or are not available may be eligible for this study Candidates may not have a tissue-matched sibling or matched unrelated donor and must have a family member who is a partial tissue type match
Participants undergo the following tests and procedures
Insertion of a central intravenous IV line plastic tube into a large vein The tube is used for giving the donated stem cells and antibiotics and other medicines for transfusions of red blood cells and platelets and for collecting blood samples
Preparatory chemotherapy fludarabine cyclophosphamide and anti-thymocyte globulin and total body irradiation to suppress immunity and prevent rejection of the donated cells
Infusion of the donated stem cells and umbilical cord cells
Immune suppression with the drugs tacrolimus mycophenolate mofetil and prednisone to prevent rejection of the donated cells and to prevent graft-versus-host disease GVHD a complication of stem cell transplants in which the donors immune cells destroy the patients healthy tissues
The average hospital stay after stem cell transplantation is 3 to 4 weeks Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation Once the patient returns home his or her referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter Patient follow-up visits are scheduled at NIH at 1 2 3 4 and 5 years after transplantation to monitor for signs of disease or post-transplantation complications such as infection or GVHD After 5 years participants are offered the opportunity to enroll in NHLBIs long-term evaluation and follow-up care protocol
Detailed Description:
Severe aplastic anemia SAA and myelodysplastic syndrome MDS are life-threatening bone marrow disorders For SAA patients long term survival can be achieved with immunosuppressive treatment However of those patients treated with immunosuppressive therapy one quarter to one third will not respond and about 50 percent of responders will relapse
Allogeneic bone marrow transplantation from either HLA-matched sibling or matched unrelated donor cures about 70 percent of patients with SAA and 30-60 percent of patients with MDS Unfortunately most patients with these disorders are not suitable candidates for hematopoietic stem cell transplantation HSCT due to advanced age or lack of a histocompatible donor For such patients transplantation using unrelated cord blood UCB has been shown to be a reasonable alternative transplant strategy The advantage to UCB transplant is the ease and rapidity of availability requirement of less than perfect HLA match and lower rates of graft versus host disease compared to mismatched bone marrow or peripheral blood stem cell transplants The major disadvantage of UCB transplantation in adults is the limited number of nucleated cells contained within the cord unit resulting in prolonged neutropenia and failure of engraftment which contributes to infection and transplant related mortality TRM In order to harness the advantage of UCB availability and to overcome the disadvantage of delayed neutrophil recovery we propose to test whether co-administration of unrelated umbilical cord blood and a relatively low number of highly purified haploidentical peripheral blood CD34 cells from a related donor might promote rapid engraftment and reduce TRM secondary to prolonged neutropenia associated with conventional umbilical cord blood transplant UCBT
This research protocol is therefore designed to evaluate the safety and effectiveness of co-infusion of unrelated umbilical cord blood and haploidentical CD34 plus cells from a related donor following nonmyeloablative conditioning for neutropenic patients with SAA or MDS with refractory anemia RA that has proven to be refractory to medical therapy Subjects will receive a novel non-myeloablative immunosuppressive conditioning regimen of cyclophosphamide fludarabine horse ATG antithymocyte globulin and one dose of total body irradiation 200cGy followed by an infusion of the allografts The haploidentical stem cell product will be T-cell depleted and enriched for CD34 plus cells using the Miltenyi CliniMacs system To reduce TRM secondary to prolonged neutropenia associated with conventional UCB transplantation haploidentical CD34 stem cells will be co-infused with a single UCB unit serologically matched at greater than or equal to 46 HLA loci
The primary endpoint is donor engraftment by day 42 defined as an ANC of greater than 500 from either the haplo donor the cord or both combined Secondary endpoints will include standard transplant outcome variables such as non-hematological toxicities incidence and severity of acute and chronic GVHD and relapse of disease We will also evaluate ANC recovery ANC greater than 500 cellsmicrol at day 22 and 100 day and 200 day treatment related mortality TRM of this novel transplant approach Health related quality of life will also be assessed pre-transplant 30 and 100 days post-transplant and every 6 months until 5 years post transplant
Allogeneic bone marrow transplantation from either HLA-matched sibling or matched unrelated donor cures about 70 percent of patients with SAA and 30-60 percent of patients with MDS Unfortunately most patients with these disorders are not suitable candidates for hematopoietic stem cell transplantation HSCT due to advanced age or lack of a histocompatible donor For such patients transplantation using unrelated cord blood UCB has been shown to be a reasonable alternative transplant strategy The advantage to UCB transplant is the ease and rapidity of availability requirement of less than perfect HLA match and lower rates of graft versus host disease compared to mismatched bone marrow or peripheral blood stem cell transplants The major disadvantage of UCB transplantation in adults is the limited number of nucleated cells contained within the cord unit resulting in prolonged neutropenia and failure of engraftment which contributes to infection and transplant related mortality TRM In order to harness the advantage of UCB availability and to overcome the disadvantage of delayed neutrophil recovery we propose to test whether co-administration of unrelated umbilical cord blood and a relatively low number of highly purified haploidentical peripheral blood CD34 cells from a related donor might promote rapid engraftment and reduce TRM secondary to prolonged neutropenia associated with conventional umbilical cord blood transplant UCBT
This research protocol is therefore designed to evaluate the safety and effectiveness of co-infusion of unrelated umbilical cord blood and haploidentical CD34 plus cells from a related donor following nonmyeloablative conditioning for neutropenic patients with SAA or MDS with refractory anemia RA that has proven to be refractory to medical therapy Subjects will receive a novel non-myeloablative immunosuppressive conditioning regimen of cyclophosphamide fludarabine horse ATG antithymocyte globulin and one dose of total body irradiation 200cGy followed by an infusion of the allografts The haploidentical stem cell product will be T-cell depleted and enriched for CD34 plus cells using the Miltenyi CliniMacs system To reduce TRM secondary to prolonged neutropenia associated with conventional UCB transplantation haploidentical CD34 stem cells will be co-infused with a single UCB unit serologically matched at greater than or equal to 46 HLA loci
The primary endpoint is donor engraftment by day 42 defined as an ANC of greater than 500 from either the haplo donor the cord or both combined Secondary endpoints will include standard transplant outcome variables such as non-hematological toxicities incidence and severity of acute and chronic GVHD and relapse of disease We will also evaluate ANC recovery ANC greater than 500 cellsmicrol at day 22 and 100 day and 200 day treatment related mortality TRM of this novel transplant approach Health related quality of life will also be assessed pre-transplant 30 and 100 days post-transplant and every 6 months until 5 years post transplant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
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 |
|---|---|---|---|
| 08-H-0046 | None | None | None |