Ignite Creation Date:
2024-05-06 @ 2:23 AM
Last Modification Date:
2024-10-26 @ 11:18 AM
Study NCT ID:
NCT02038478
Status:
WITHDRAWN
Last Update Posted:
2021-07-29
First Post:
2014-01-10
Brief Title:
Allograft for Sickle Cell Disease and Thalassemia
Sponsor:
University of Texas Southwestern Medical Center
Organization:
University of Texas Southwestern Medical Center
Study Overview
Official Title:
Nonmyeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Severe Congenital Anemias Including Sickle Cell Disease and Thalassemia
Status:
WITHDRAWN
Status Verified Date:
2021-07
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:
The design of the study incorporates the following features
1 This is a phase II study to determine the safety and therapeutic potential of a new transplant approach disease-free survival graft versus myeloma effect and to evaluate its toxicity profile immediate toxicity graft-versus-host disease graft rejection mortality in a patient population with severe congenital anemias
2 The patient cohort to be studied Those patients with severe sickle cell disease and thalassemia who have risk factors for high mortality and morbidity related to their disease
3 Transplant Conditioning Regimen - Immunosuppression without myeloablation Patients will receive conditioning sufficient to allow donor lympho-hematopoietic engraftment without complete marrow ablation If the graft is rejected the patient will reconstitute autologous marrow function We will use a combination of low dose irradiation Alemtuzumab Campath and sirolimus
4 Peripheral blood hematopoietic progenitor cell PBPC transplant An unmanipulated peripheral blood stem cell collection from a filgrastim G-CSF stimulated HLA-matched donor should improve the chance of engraftment because of the high stem cell dose 5 x 106kg CD34 cells and the presence of donor lymphocytes To reduce the risk of GVHD patients will receive sirolimus before and after the transplant The sirolimus will be tapered as necessary to minimize any graft versus host disease while still maintaining adequate chimerism
1 This is a phase II study to determine the safety and therapeutic potential of a new transplant approach disease-free survival graft versus myeloma effect and to evaluate its toxicity profile immediate toxicity graft-versus-host disease graft rejection mortality in a patient population with severe congenital anemias
2 The patient cohort to be studied Those patients with severe sickle cell disease and thalassemia who have risk factors for high mortality and morbidity related to their disease
3 Transplant Conditioning Regimen - Immunosuppression without myeloablation Patients will receive conditioning sufficient to allow donor lympho-hematopoietic engraftment without complete marrow ablation If the graft is rejected the patient will reconstitute autologous marrow function We will use a combination of low dose irradiation Alemtuzumab Campath and sirolimus
4 Peripheral blood hematopoietic progenitor cell PBPC transplant An unmanipulated peripheral blood stem cell collection from a filgrastim G-CSF stimulated HLA-matched donor should improve the chance of engraftment because of the high stem cell dose 5 x 106kg CD34 cells and the presence of donor lymphocytes To reduce the risk of GVHD patients will receive sirolimus before and after the transplant The sirolimus will be tapered as necessary to minimize any graft versus host disease while still maintaining adequate chimerism
Detailed Description:
A human lymphocyte antigen HLA-matched sibling donor will receive filgrastim G-CSF 10 to16 µgkgd subcutaneously or intravenously for up to 6 days with apheresis collections of PBPC on day 5 and day 6 if required The product will be collected by leukophoresis with a goal of 10 x 106 CD34 cellskg with a minimum of 5 x 106 CD34 cellskg
The patient will receive a preparative regimen of Alemtuzumab to be infused on days -7 to -3 followed by 300 cGy TBI given as a single dose on day -2 Sirolimus at a dose of 5mgday to maintain trough levels between 10-15ngml will be started on day -1 The PBPC graft targeted to deliver 10 x 106 CD34 cellskg at minimum 5 x 106 CD34 cellskg will be infused on day 0 On days 14 30 60 and 100 the chimeric status of patients will be assessed by microsatellite analysis of the peripheral blood More frequent monitoring may be required
Sickle cell patients with pulmonary hypertension will meet with a Pulmonary Medicine Consult to determine appropriate management prior to SCT
Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen
Iron chelation must be discontinued 48 hours before initiating the conditioning regimen
Hydroxyurea must be discontinued one day prior to initiating the conditioning regimen
The patient will receive a preparative regimen of Alemtuzumab to be infused on days -7 to -3 followed by 300 cGy TBI given as a single dose on day -2 Sirolimus at a dose of 5mgday to maintain trough levels between 10-15ngml will be started on day -1 The PBPC graft targeted to deliver 10 x 106 CD34 cellskg at minimum 5 x 106 CD34 cellskg will be infused on day 0 On days 14 30 60 and 100 the chimeric status of patients will be assessed by microsatellite analysis of the peripheral blood More frequent monitoring may be required
Sickle cell patients with pulmonary hypertension will meet with a Pulmonary Medicine Consult to determine appropriate management prior to SCT
Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen
Iron chelation must be discontinued 48 hours before initiating the conditioning regimen
Hydroxyurea must be discontinued one day prior to initiating the conditioning regimen
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