Ignite Creation Date:
2024-05-05 @ 4:35 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00260689
Status:
COMPLETED
Last Update Posted:
2017-06-08
First Post:
2005-12-01
Brief Title:
Three Immunosuppressive Treatment Regimens for Severe Aplastic Anemia
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Study of Three Immunosuppressive Regimens in Treatment Naive Patients With Severe Aplastic Anemia Horse ATGCsA Taper vs Rabbit-ATGCsA vs Alemtuzumab
Status:
COMPLETED
Status Verified Date:
2017-05-15
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:
Severe aplastic anemia SAA is a life-threatening bone marrow failure disorder characterized by pancytopenia and a hypocellular bone marrow Allogeneic bone marrow transplantation offers the opportunity for cure in 70 of patients but most patients are not suitable candidates for hematopoietic stem cell transplantation HSCT due to advanced age or lack of a histocompatible donor For these patients comparable long term survival is attainable with immunosuppressive treatment with anti-thymocyte globulin ATG and cyclosporine CsA However of those patients treated with horse ATGh-ATGCsA one quarter to one third will not respond and about 50 of responders relapse Auto-reactive T cells may be resistant to the effect of ATGCsA non-responders while in others residual auto-reactive T cells expand post-treatment leading to hematopoietic stem cell destruction and recurrent pancytopenia relapse As long term survival is correlated to response rates and robustness of hematopoietic recovery novel immunosuppressive regimens that can achieve hematologic response and decrease relapse rates are needed
This trial will compare the effectiveness of three immunosuppressive regimens as first line therapies in patients with SAA with early hematologic response as the primary endpoint as well as assess the role of extended CsA treatment after h-ATG in reducing numbers of late events of relapse and clonal evolution Randomization is employed to obtain an equal distribution of subject to each arm comparisons of early hematologic responses will be made among the rates observed among the three concurrent arms rabbit-ATG r-ATG versus standard h-ATG alemtuzumab vs standard h-ATG For long course CSA comparison of primary end points will be to well established historic relapse rate of 38 at 2-3 years and a cumulative rate of clonal evolution of 15
This trial will compare the effectiveness of three immunosuppressive regimens as first line therapies in patients with SAA with early hematologic response as the primary endpoint as well as assess the role of extended CsA treatment after h-ATG in reducing numbers of late events of relapse and clonal evolution Randomization is employed to obtain an equal distribution of subject to each arm comparisons of early hematologic responses will be made among the rates observed among the three concurrent arms rabbit-ATG r-ATG versus standard h-ATG alemtuzumab vs standard h-ATG For long course CSA comparison of primary end points will be to well established historic relapse rate of 38 at 2-3 years and a cumulative rate of clonal evolution of 15
Detailed Description:
Severe aplastic anemia SAA is a life-threatening bone marrow failure disorder characterized by pancytopenia and a hypocellular bone marrow Allogeneic bone marrow transplantation offers the opportunity for cure in 70 of patients but most patients are not suitable candidates for hematopoietic stem cell transplantation HSCT due to advanced age or lack of a histocompatible donor For these patients comparable long term survival is attainable with immunosuppressive treatment with anti-thymocyte globulin ATG and cyclosporine CsA However of those patients treated with horse ATGh-ATGCsA one quarter to one third will not respond and about 50 of responders relapse Auto-reactive T cells may be resistant to the effect of ATGCsA non-responders while in others residual auto-reactive T cells expand post-treatment leading to hematopoietic stem cell destruction and recurrent pancytopenia relapse As long term survival is correlated to response rates and robustness of hematopoietic recovery novel immunosuppressive regimens that can achieve hematologic response and decrease relapse rates are needed
This trial will compare the effectiveness of three immunosuppressive regimens as first line therapies in patients with SAA with early hematologic response as the primary endpoint as well as assess the role of extended CsA treatment after h-ATG in reducing numbers of late events of relapse and clonal evolution Randomization is employed to obtain an equal distribution of subject to each arm comparisons of early hematologic responses will be made among the rates observed among the three concurrent arms rabbit-ATG r-ATG versus standard h-ATG alemtuzumab vs standard h-ATG For long course CSA comparison of primary end points will be to well established historic relapse rate of 38 at 2-3 years and a cumulative rate of clonal evolution of 15
In the original design subjects were randomized to one of three different regimens h-ATG 6 months CsA followed by an 18 month CsA taper r-ATG 6 months CsA or alemtuzumab Campath Subjects failing to respond to r-ATG will be crossed over to alemtuzumab Campath and subjects failing alemtuzumab Campath will be crossed over to r-ATG Subjects failing to respond to h-ATG CsA taper will go off study and be evaluated for eligibility for a second course of immunosuppression on companion protocol 03-H-0249 which similarly randomizes subjects between r-ATG and alemtuzumab Campath as salvage therapy
The Campath arm was closed to new accrual for lack of efficacy on 4102008 Subsequently new accruals will be randomized to h-ATG 6 months CsA followed by an 18 month CsA taper or r-ATG 6 months CsA Subjects failing to respond to h-ATG CsA taper will go off study and be evaluated for eligibility for a second course of immunosuppression on companion protocol 03-H-0249 which similarly randomizes subjects between r-ATG and alemtuzumab Campath as salvage therapy Subjects who fail to respond to r-ATG 6 months CsA will be offered treatment with h-ATG as salvage therapy or will go off-study to alternative treatments or stem cell transplant from sibling or unrelated donor
The primary endpoint will be hematologic response defined as no longer meeting criteria for SAA at 6 months Secondary endpoints are relapse robustness of hematologic recovery at 6 months response at 3 and 12 months survival clonal evolution to PNH myelodysplasia and acute leukemia Long-course CSA will be assessed separately for its efficacy in reducing late events of relapse and evolution by comparison to historical control data
This trial will compare the effectiveness of three immunosuppressive regimens as first line therapies in patients with SAA with early hematologic response as the primary endpoint as well as assess the role of extended CsA treatment after h-ATG in reducing numbers of late events of relapse and clonal evolution Randomization is employed to obtain an equal distribution of subject to each arm comparisons of early hematologic responses will be made among the rates observed among the three concurrent arms rabbit-ATG r-ATG versus standard h-ATG alemtuzumab vs standard h-ATG For long course CSA comparison of primary end points will be to well established historic relapse rate of 38 at 2-3 years and a cumulative rate of clonal evolution of 15
In the original design subjects were randomized to one of three different regimens h-ATG 6 months CsA followed by an 18 month CsA taper r-ATG 6 months CsA or alemtuzumab Campath Subjects failing to respond to r-ATG will be crossed over to alemtuzumab Campath and subjects failing alemtuzumab Campath will be crossed over to r-ATG Subjects failing to respond to h-ATG CsA taper will go off study and be evaluated for eligibility for a second course of immunosuppression on companion protocol 03-H-0249 which similarly randomizes subjects between r-ATG and alemtuzumab Campath as salvage therapy
The Campath arm was closed to new accrual for lack of efficacy on 4102008 Subsequently new accruals will be randomized to h-ATG 6 months CsA followed by an 18 month CsA taper or r-ATG 6 months CsA Subjects failing to respond to h-ATG CsA taper will go off study and be evaluated for eligibility for a second course of immunosuppression on companion protocol 03-H-0249 which similarly randomizes subjects between r-ATG and alemtuzumab Campath as salvage therapy Subjects who fail to respond to r-ATG 6 months CsA will be offered treatment with h-ATG as salvage therapy or will go off-study to alternative treatments or stem cell transplant from sibling or unrelated donor
The primary endpoint will be hematologic response defined as no longer meeting criteria for SAA at 6 months Secondary endpoints are relapse robustness of hematologic recovery at 6 months response at 3 and 12 months survival clonal evolution to PNH myelodysplasia and acute leukemia Long-course CSA will be assessed separately for its efficacy in reducing late events of relapse and evolution by comparison to historical control data
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 |
|---|---|---|---|
| 06-H-0034 | OTHER | NIH | None |