Ignite Creation Date:
2024-05-05 @ 11:30 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00061568
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-02-29
First Post:
2003-05-29
Brief Title:
Improving the Results of Bone Marrow Transplantation for Patients With Severe Congenital Anemias
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Nonmyeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Severe Congenital Anemias Including Sickle Cell Disease SCD and B-Thalassemia
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-02
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:
People with severe congenital anemias such as sickle cell anemia and beta-thalassemia have been cured with bone marrow transplantation BMT The procedure however is limited to children younger than the age of 16 because the risks are lower for children than for adults
The purpose of this study is to explore the use of a BMT regimen that instead of chemotherapy uses a low dose of radiation combined with two immunosuppressive drugs This type BMT procedure is described as nonmyeloablative meaning that it does not destroy the patient s bone marrow It is hoped that this type of BMT will be safe for patients normally excluded from the procedure because of their age and other reasons
To participate in this study patients must be between the ages of 18 and 65 and have a sibling who is a well-matched stem-cell donor Beyond the standard BMT protocol study participants will undergo additional procedures The donor will receive G-CSF by injection for five days then his or her stem cells will be collected and frozen one month prior to BMT Approximately one month later the patient will be given two immune-suppressing drugs Campath 1-H and Sirolimus as well as a single low dose of total body irradiation and then the cells from the donor will be infused
Prior to their participation in this study patients will undergo the following evaluations a physical exam blood work breathing tests heart-function tests chest and sinus x-rays and bone-marrow sampling
The purpose of this study is to explore the use of a BMT regimen that instead of chemotherapy uses a low dose of radiation combined with two immunosuppressive drugs This type BMT procedure is described as nonmyeloablative meaning that it does not destroy the patient s bone marrow It is hoped that this type of BMT will be safe for patients normally excluded from the procedure because of their age and other reasons
To participate in this study patients must be between the ages of 18 and 65 and have a sibling who is a well-matched stem-cell donor Beyond the standard BMT protocol study participants will undergo additional procedures The donor will receive G-CSF by injection for five days then his or her stem cells will be collected and frozen one month prior to BMT Approximately one month later the patient will be given two immune-suppressing drugs Campath 1-H and Sirolimus as well as a single low dose of total body irradiation and then the cells from the donor will be infused
Prior to their participation in this study patients will undergo the following evaluations a physical exam blood work breathing tests heart-function tests chest and sinus x-rays and bone-marrow sampling
Detailed Description:
Nonmyeloablative allogeneic peripheral blood stem cell PBSC transplants are currently being investigated in phase III trials assessing engraftment efficacy and toxicity at a number of transplant centers Preliminary data have shown a high rate of complete donor engraftment with a relatively low toxicity profile The decreased risk of transplant-related complications associated with nonmyeloablative transplants expands eligibility to patients with nonmalignant hematological disorders curable by allogeneic transplantation however significant toxicity with current regimens persists including severe graft versus host disease GVHD leading to significant morbidity and mortality Moreover mixed chimerism has been shown to be sufficient to induce clinical remissions in children with nonmalignant hematologic disorders undergoing conventional allogeneic transplantation Therefore newer regimens need to be developed that are more applicable to patients with non-malignant disorders in whom no graft vs leukemia effect is needed and where mixed chimerism is sufficient for disease amelioration
In this protocol we propose transplantation in patients with severe beta-globin disorders including sickle cell disease SCD and beta-thalassemia considered at high risk for complications from or ineligible for standard BMT with allogeneic PBSCs from an HLA identical sibling using a novel immunosuppressive regimen without myeloablation in an attempt to further decrease the transplant related morbiditymortality The low intensity nonmyeloablative conditioning regimen will consist of low dose radiation Alemtuzumab Campath and Sirolimus Rapamune as a strategy to provide adequate immunosuppression to allow sufficient engraftment for clinical remission with a lower risk of GVHD development T-cell replete donor-derived granulocyte colony stimulating factor filgrastim G-CSF mobilized PBSCs will be used to establish hematopoietic and lymphoid reconstitution
The primary endpoint of this study is treatment success at one year defined as full donor type hemoglobin on hemoglobin electrophoresis for patients with SCD and transfusion-independence for patients with beta-thalassemia Other end points include degree of donor-host chimerism necessary for long-term graft survival and disease amelioration incidence of acute and chronic graft-vs-host disease GVHD incidence of graft rejection transplant related morbidity as well as disease-free and overall survival
In this protocol we propose transplantation in patients with severe beta-globin disorders including sickle cell disease SCD and beta-thalassemia considered at high risk for complications from or ineligible for standard BMT with allogeneic PBSCs from an HLA identical sibling using a novel immunosuppressive regimen without myeloablation in an attempt to further decrease the transplant related morbiditymortality The low intensity nonmyeloablative conditioning regimen will consist of low dose radiation Alemtuzumab Campath and Sirolimus Rapamune as a strategy to provide adequate immunosuppression to allow sufficient engraftment for clinical remission with a lower risk of GVHD development T-cell replete donor-derived granulocyte colony stimulating factor filgrastim G-CSF mobilized PBSCs will be used to establish hematopoietic and lymphoid reconstitution
The primary endpoint of this study is treatment success at one year defined as full donor type hemoglobin on hemoglobin electrophoresis for patients with SCD and transfusion-independence for patients with beta-thalassemia Other end points include degree of donor-host chimerism necessary for long-term graft survival and disease amelioration incidence of acute and chronic graft-vs-host disease GVHD incidence of graft rejection transplant related morbidity as well as disease-free and overall survival
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 |
|---|---|---|---|
| 03-H-0170 | None | None | None |