Ignite Creation Date:
2024-05-06 @ 9:24 AM
Last Modification Date:
2024-10-26 @ 12:14 PM
Study NCT ID:
NCT02979873
Status:
RECRUITING
Last Update Posted:
2024-06-13
First Post:
2016-12-01
Brief Title:
Sirolimus Rapamune for Relapse Prevention in People With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Trial of Sirolimus RapamuneR for Relapse Prevention in Patients With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy
Status:
RECRUITING
Status Verified Date:
2024-09-05
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
People with severe aplastic anemia SAA do not make enough red and white blood cells andor platelets Their bodys immune system stops the bone marrow from making these cells The treatment cyclosporine leads to better blood counts But when this treatment is stopped the disease may return in 1 in 3 people The drug sirolimus may help by suppressing the immune system
Objective
To evaluate and compare the usefulness of sirolimus in preventing aplastic anemia from returning after cyclosporine is stopped compared with stopping cyclosporine alone
Eligibility
People ages 2 and older with SAA who
Have responded to immunosuppressive therapy that includes cyclosporine and continue to take cyclosporine
Are not taking drugs with hematologic effects
Design
Participants will be screened with
Medical history
Physical exam
Blood and urine tests
Bone marrow biopsy The area above the hipbone will be numbed A thin needle will remove
some bone marrow
Participants will be randomly assigned to a group All will stop cyclosporine Group 1 will take sirolimus by mouth at the same time each day for 3 months with close monitoring Group 2 will not receive the study drug but will be monitored closely
Participants will have clinical tests for the first 3 months
Weekly blood test
Monthly fasting blood test
For group 1 measurements of sirolimus in the blood every 1 2 weeks
Participants will have clinic visits at 3 months 12 months and annually for 5 years after the study starts They may have another visit if their SAA returns These will include
Blood and urine tests
Bone marrow biopsy
People with severe aplastic anemia SAA do not make enough red and white blood cells andor platelets Their bodys immune system stops the bone marrow from making these cells The treatment cyclosporine leads to better blood counts But when this treatment is stopped the disease may return in 1 in 3 people The drug sirolimus may help by suppressing the immune system
Objective
To evaluate and compare the usefulness of sirolimus in preventing aplastic anemia from returning after cyclosporine is stopped compared with stopping cyclosporine alone
Eligibility
People ages 2 and older with SAA who
Have responded to immunosuppressive therapy that includes cyclosporine and continue to take cyclosporine
Are not taking drugs with hematologic effects
Design
Participants will be screened with
Medical history
Physical exam
Blood and urine tests
Bone marrow biopsy The area above the hipbone will be numbed A thin needle will remove
some bone marrow
Participants will be randomly assigned to a group All will stop cyclosporine Group 1 will take sirolimus by mouth at the same time each day for 3 months with close monitoring Group 2 will not receive the study drug but will be monitored closely
Participants will have clinical tests for the first 3 months
Weekly blood test
Monthly fasting blood test
For group 1 measurements of sirolimus in the blood every 1 2 weeks
Participants will have clinic visits at 3 months 12 months and annually for 5 years after the study starts They may have another visit if their SAA returns These will include
Blood and urine tests
Bone marrow biopsy
Detailed Description:
Most acquired aplastic anemia ensues from immune-mediated destruction of hematopoietic stem and progenitor cells
Immunosuppression is the definitive treatment of patients with acquired aplastic anemia who are not candidates for immediate hematopoietic stem cell transplantation
Horse ATG combined with the calcineurin inhibitor cyclosporine CsA remains standard as first-line immunosuppressive therapy IST
Hematologic responses to transfusion independence occur in about two thirds of patients with standard IST and in 80-90 of patients treated with IST in combination with the growth factor eltrombopag
About 30 to 40 of patients relapse after discontinuation of cyclosporineMany achieve disease control after the reinitiation of CSA but remain CSA dependent indefinitely
Evidence from mouse models of bone marrow failure indicates that conversion from cyclosporine to the mTOR inhibitor sirolimus SRL results in immune tolerance which can endure the eventual withdrawal of SRL
We hypothesize that CSA to SRL conversion will significantly decrease the relapse rate after immunosuppressive therapy for acquired aplastic anemia
This study will investigate the safety and efficacy of SRL for preventing relapse in patients -previously treated with IST who remain on CSA The primary endpoint is rate of relapse at 2 years following conversion from CSA to SRL versus stopping CSA
Biological sampling of peripheral blood and bone marrow aspirates during treatment will be used to investigate changes to lymphocyte phenotypes and cytokine profiles
Immunosuppression is the definitive treatment of patients with acquired aplastic anemia who are not candidates for immediate hematopoietic stem cell transplantation
Horse ATG combined with the calcineurin inhibitor cyclosporine CsA remains standard as first-line immunosuppressive therapy IST
Hematologic responses to transfusion independence occur in about two thirds of patients with standard IST and in 80-90 of patients treated with IST in combination with the growth factor eltrombopag
About 30 to 40 of patients relapse after discontinuation of cyclosporineMany achieve disease control after the reinitiation of CSA but remain CSA dependent indefinitely
Evidence from mouse models of bone marrow failure indicates that conversion from cyclosporine to the mTOR inhibitor sirolimus SRL results in immune tolerance which can endure the eventual withdrawal of SRL
We hypothesize that CSA to SRL conversion will significantly decrease the relapse rate after immunosuppressive therapy for acquired aplastic anemia
This study will investigate the safety and efficacy of SRL for preventing relapse in patients -previously treated with IST who remain on CSA The primary endpoint is rate of relapse at 2 years following conversion from CSA to SRL versus stopping CSA
Biological sampling of peripheral blood and bone marrow aspirates during treatment will be used to investigate changes to lymphocyte phenotypes and cytokine profiles
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 |
|---|---|---|---|
| 17-H-0019 | None | None | None |