Ignite Creation Date:
2024-05-05 @ 10:43 PM
Last Modification Date:
2024-10-26 @ 10:23 AM
Study NCT ID:
NCT01174108
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2010-07-31
Brief Title:
Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34 Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34 Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-Cells
Status:
RECRUITING
Status Verified Date:
2024-09-19
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:
Background
Stem cell transplants from related donors allogenic stem cell transplants can be used to treat individuals with certain kinds of severe blood diseases or cancers such as severe anemia Allogenic stem cell transplants encourage the growth of new bone marrow to replace that of the recipient Because stem cell transplants can have serious complications researchers are interested in developing new approaches to stem cell transplants that will reduce the likelihood of these complications
By reducing the number of white blood cells included in the blood taken during the stem cell collection process and replacing them with a smaller amount of white blood cells collected prior to stem cell donation the stem cell transplant may be less likely to cause severe complications for the recipient Researchers are investigating whether altering the stem cell transplant donation procedure in this manner will improve the likelihood of a successful stem cell transplant with fewer complications
Objectives
- To evaluate a new method of stem cell transplantation that may reduce the possibly of severe side effects or transplant rejection in the recipient
Eligibility
Recipient Individuals between 4 and 80 years of age who have been diagnosed with a blood disease that can be treated with allogenic stem cell transplants
Donor Individuals between 4 and 80 years of age who are related to the recipient and are eligible to donate blood OR unrelated donors found through the National Marrow Donor Program
Design
All participants will be screened with a physical examination and medical history
DONORS
Donors will undergo an initial apheresis procedure to donate white blood cells
After the initial donation donors will receive injections of filgrastim to release bone marrow cells into the blood
After 5 days of filgrastim injections donors will have apheresis again to donate stem cells that are present in the blood
RECIPIENTS
Recipients will provide an initial donation of white blood cells to be used for research purposes only
From 7 days before the stem cell transplant participants will be admitted to the inpatient unit of the National Institutes of Health Clinical Center and will receive regular doses of cyclophosphamide fludarabine and anti-thymocyte globulin to suppress their immune system and prepare for the transplant
After the initial chemotherapy participants will receive the donated white blood cells and stem cells as a single infusion
After the stem cell and white blood cell transplant participants will have regular doses of cyclosporine and methotrexate to prevent rejection of the donor cells Participants will have three doses of methotrexate within the week after the transplant but will continue to take cyclosporine for up to 4 months after the transplant
Participants will remain in inpatient care for up to 1 month after the transplant and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects
Stem cell transplants from related donors allogenic stem cell transplants can be used to treat individuals with certain kinds of severe blood diseases or cancers such as severe anemia Allogenic stem cell transplants encourage the growth of new bone marrow to replace that of the recipient Because stem cell transplants can have serious complications researchers are interested in developing new approaches to stem cell transplants that will reduce the likelihood of these complications
By reducing the number of white blood cells included in the blood taken during the stem cell collection process and replacing them with a smaller amount of white blood cells collected prior to stem cell donation the stem cell transplant may be less likely to cause severe complications for the recipient Researchers are investigating whether altering the stem cell transplant donation procedure in this manner will improve the likelihood of a successful stem cell transplant with fewer complications
Objectives
- To evaluate a new method of stem cell transplantation that may reduce the possibly of severe side effects or transplant rejection in the recipient
Eligibility
Recipient Individuals between 4 and 80 years of age who have been diagnosed with a blood disease that can be treated with allogenic stem cell transplants
Donor Individuals between 4 and 80 years of age who are related to the recipient and are eligible to donate blood OR unrelated donors found through the National Marrow Donor Program
Design
All participants will be screened with a physical examination and medical history
DONORS
Donors will undergo an initial apheresis procedure to donate white blood cells
After the initial donation donors will receive injections of filgrastim to release bone marrow cells into the blood
After 5 days of filgrastim injections donors will have apheresis again to donate stem cells that are present in the blood
RECIPIENTS
Recipients will provide an initial donation of white blood cells to be used for research purposes only
From 7 days before the stem cell transplant participants will be admitted to the inpatient unit of the National Institutes of Health Clinical Center and will receive regular doses of cyclophosphamide fludarabine and anti-thymocyte globulin to suppress their immune system and prepare for the transplant
After the initial chemotherapy participants will receive the donated white blood cells and stem cells as a single infusion
After the stem cell and white blood cell transplant participants will have regular doses of cyclosporine and methotrexate to prevent rejection of the donor cells Participants will have three doses of methotrexate within the week after the transplant but will continue to take cyclosporine for up to 4 months after the transplant
Participants will remain in inpatient care for up to 1 month after the transplant and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects
Detailed Description:
Allogeneic hematopoietic stem cell transplantation aHSCT can cure patients with a variety of bone marrow failure syndromes BMFS including severe aplastic anemia SAA paroxysmal nocturnal hemoglobinuria PNH or myelodysplastic syndrome MDS associated with cytopenias Patients with BMFS have traditionally been transplanted with bone marrow BM as a stem cell source Although chronic graft versus host disease cGVHD occurs less commonly with BM compared to filgrastim G-CSF mobilized peripheral blood stem cell PBSC transplants BM allografts have lower CD34 progenitor cell numbers which increases the risk of graft rejection in heavily transfused BMFS patients to 15-20 To overcome this risk our group developed a novel transplant approach for patients at high risk for graft rejection that utilized cyclophosphamide fludarabine and anti-thymocyte globulin ATG conditioning followed by infusion of a CD34 cell rich T-cell replete G-CSF mobilized PBSC allograft Remarkably in 56 consecutive BMFS patients who had multiple risk factors for graft rejection who underwent this transplant approach graft rejection did not occur with all patients achieving complete donor lymphohematopoietic chimerism Unfortunately recipients of G-CSF mobilized PBSC had a higher incidence of cGVHD than has historically been observed with BM transplantation 72 vs 50 cumulative incidence of cGVHD at 1 year respectively G-CSF mobilized PBSC transplants contained approximately a 20 fold higher dose of T-cells that had undergone a TH-2 type cytokine polarization a factor which likely contributed to this high incidence of cGVHD In this protocol we attempt to prevent graft failure and to reduce the incidence of cGVHD by transplanting high numbers of CD34 selected PBSC co-infused with a reduced dose of non-mobilized donor T-cells that have not undergone a TH-2 cytokine polarization
Subjects with BMFS at high risk for graft rejection will undergo allogeneic stem cell transplantation from an HLA identical sibling or match unrelated donor using the identical conditioning regimen utilized in protocol 99- H-0050 Using the Miltenyi CliniMACs system recipients will receive an allograft on day 0 containing donor CD34 cells that have been positively selected and T-cell depleted following G-CSF mobilization goal CD34 cell dose of 5 x 106 CD34 cells kg recipient combined with 2 x 107 cellskg of non-mobilized CD3 T-cells previously collected and cryopreserved from the same donor by apheresis prior to G-CSF mobilization
Primary objective To evaluate whether administering a CD34 selected T-cell depleted peripheral blood stem cell graft with a concomitant infusion of non-mobilized donor T-cells at a dose that matches the T-cell dose that is infused in historical bone marrow transplant cohorts will reduce the incidence of cGVHD at 1 year to that observed with a conventional bone marrow transplant 50 without increasing the risk of graft failure This trial design will allow the trial to stop early if it is unlikely that we have reduced the proportion of one year cGVHD to 50 or if the combined event rate for failed donor engraftment or treatment related mortality TRM at day 100 exceeds 20
The primary endpoint of this study will be cGVHD at day 365
Secondary end points include transplant related mortality engraftment degree of donor-host chimerism incidence of acute and chronic graft versus host disease cGVHD transplant related morbidity and overall survival Health related quality of life will also be assessed as a secondary outcome measure pre-transplant 30 and 100 days post transplant and every 6 months until 5 years post transplant
Subjects with BMFS at high risk for graft rejection will undergo allogeneic stem cell transplantation from an HLA identical sibling or match unrelated donor using the identical conditioning regimen utilized in protocol 99- H-0050 Using the Miltenyi CliniMACs system recipients will receive an allograft on day 0 containing donor CD34 cells that have been positively selected and T-cell depleted following G-CSF mobilization goal CD34 cell dose of 5 x 106 CD34 cells kg recipient combined with 2 x 107 cellskg of non-mobilized CD3 T-cells previously collected and cryopreserved from the same donor by apheresis prior to G-CSF mobilization
Primary objective To evaluate whether administering a CD34 selected T-cell depleted peripheral blood stem cell graft with a concomitant infusion of non-mobilized donor T-cells at a dose that matches the T-cell dose that is infused in historical bone marrow transplant cohorts will reduce the incidence of cGVHD at 1 year to that observed with a conventional bone marrow transplant 50 without increasing the risk of graft failure This trial design will allow the trial to stop early if it is unlikely that we have reduced the proportion of one year cGVHD to 50 or if the combined event rate for failed donor engraftment or treatment related mortality TRM at day 100 exceeds 20
The primary endpoint of this study will be cGVHD at day 365
Secondary end points include transplant related mortality engraftment degree of donor-host chimerism incidence of acute and chronic graft versus host disease cGVHD transplant related morbidity and overall survival Health related quality of life will also be assessed as a secondary outcome measure 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?:
False
Is a FDA Regulated Device?:
True
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 |
|---|---|---|---|
| 10-H-0154 | None | None | None |