Ignite Creation Date:
2024-05-05 @ 9:45 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001962
Status:
TERMINATED
Last Update Posted:
2021-07-09
First Post:
2000-01-18
Brief Title:
A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Study of Recombinant Humanized Anti-Interleukin IL-2 Receptor Antibody Daclizumab in Patients With Moderate Aplastic Anemia Pure Red Cell Aplasia or Diamond Blackfan Anemia
Status:
TERMINATED
Status Verified Date:
2015-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
DSMB recommended closing the study and publishing the results
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Participants in this study are suffering from rare and serious blood disorders In aplastic anemia the bone marrow stops producing red blood cells platelets and white blood cells In pure red cell aplasia the bone marrow stops producing red cells and in amegakaryocytic thrombocytopenic purpura the bone marrow stops producing platelets
Current treatment approaches for these disorders include bone marrow transplant andor immunosuppression However bone marrow transplant is not always possible and immunosuppression has serious side effects
This study will investigate whether daclizumab can be used to treat these disorders Daclizumab is a genetically engineered human antibody that blocks the interleukin-2 receptor on immune cells It has been used successfully in many transplant patients to reduce the rate of organ rejection
Participants will undergo a complete history and physical examination A bone marrow aspiration and biopsy will be performed to confirm the type of bone marrow failure About 5 tablespoons of blood will be drawn for baseline tests and research purposes Daclizumab will be administered every 2 weeks by vein in a 30-minute infusion The first dose will be given at NIH and the next four may be given at NIH or by the participants primary hematologist The treatment will last 8 weeks Participants must also see their referring physician or NIH physicians every 2 weeks for blood counts In the fourth and eighth weeks of the study and at the 3-month follow-up visit 2 tablespoons of blood will be drawn at NIH At the 1-month follow-up visit to NIH 5 tablespoons of blood will be drawn and another bone marrow aspiration and biopsy performed
Risks from bone marrow aspiration and biopsy and blood draws include discomfort Daclizumab is usually well-tolerated however it may weaken immunity against certain bacteria and viruses
Current treatment approaches for these disorders include bone marrow transplant andor immunosuppression However bone marrow transplant is not always possible and immunosuppression has serious side effects
This study will investigate whether daclizumab can be used to treat these disorders Daclizumab is a genetically engineered human antibody that blocks the interleukin-2 receptor on immune cells It has been used successfully in many transplant patients to reduce the rate of organ rejection
Participants will undergo a complete history and physical examination A bone marrow aspiration and biopsy will be performed to confirm the type of bone marrow failure About 5 tablespoons of blood will be drawn for baseline tests and research purposes Daclizumab will be administered every 2 weeks by vein in a 30-minute infusion The first dose will be given at NIH and the next four may be given at NIH or by the participants primary hematologist The treatment will last 8 weeks Participants must also see their referring physician or NIH physicians every 2 weeks for blood counts In the fourth and eighth weeks of the study and at the 3-month follow-up visit 2 tablespoons of blood will be drawn at NIH At the 1-month follow-up visit to NIH 5 tablespoons of blood will be drawn and another bone marrow aspiration and biopsy performed
Risks from bone marrow aspiration and biopsy and blood draws include discomfort Daclizumab is usually well-tolerated however it may weaken immunity against certain bacteria and viruses
Detailed Description:
Many bone marrow failure syndromes in humans are now recognized to result from immunological mechanisms These diseases include aplastic anemia single hematopoietic lineage failures such as pure red cell aplasia Diamond Blackfan Anemia agranulocytosis and amegakaryocytic thrombocytopenic purpura and some types of myelodysplasia Patients with these conditions who may suffer variable degrees of anemia leukocytopenia and thrombocytopenia alone or combination have been shown to respond to a wide variety of immunosuppressive agents ranging from corticosteroids to cyclosporine CSA and antithymocyte globulin ATG However except for severe aplastic anemia which has been shown to be appropriately treated with either bone marrow transplantation or a combination of ATG and CSA single agents or regimens have usually not been applied systematically to other immune-mediated hematologic diseases In an effort to discover other and especially less toxic treatments for immunologically-mediated bone marrow diseases we seek to apply a new therapy a humanized anti-interleukin-2 receptor lL-2R monoclonal antibody mAb to a subset of patients with bone marrow failure Anti-IL-2R mAb acts against activated lymphocytes thus sharing an important mechanism of action with ATG However the mAb is much less toxic than ATG and may be administered to outpatients at relatively infrequent intervals every 2 weeks
The primary objective is to test the efficacy of anti-IL-2R mAb daclizumab we propose to treat four groups of patients 1 moderate aplastic anemia 2 single lineage failure states including pure red cell aplasia or Diamond Blackfan anemia 3 relapse of severe aplastic anemia and 4 refractory severe aplastic anemia not responding to both horse and rabbit ATGCsA Subjects will receive daclizumab once every other week for a total of 5 doses Patients relapsing after response to initial treatment may be treated with 2 additional courses of daclizumab In November 2005 the relapsed and refractory severe aplastic anemia arms were closed by the Data and Safety Monitoring Board DSMB for lack of efficacy In October 2008 the moderate aplastic anemia arm was closed by the DSMB when the data was determined sufficient for making statistical inferences regarding the original hypotheses In October 2008 accrual to the Diamond Blackfan anemia arm was closed by the DSMB for lack of accrual
The Primary endpoint is hematologic response at 3 months Secondary endpoints include transfusion dependence overall survival life threatening toxicity transformation-free survival and response duration
The primary objective is to test the efficacy of anti-IL-2R mAb daclizumab we propose to treat four groups of patients 1 moderate aplastic anemia 2 single lineage failure states including pure red cell aplasia or Diamond Blackfan anemia 3 relapse of severe aplastic anemia and 4 refractory severe aplastic anemia not responding to both horse and rabbit ATGCsA Subjects will receive daclizumab once every other week for a total of 5 doses Patients relapsing after response to initial treatment may be treated with 2 additional courses of daclizumab In November 2005 the relapsed and refractory severe aplastic anemia arms were closed by the Data and Safety Monitoring Board DSMB for lack of efficacy In October 2008 the moderate aplastic anemia arm was closed by the DSMB when the data was determined sufficient for making statistical inferences regarding the original hypotheses In October 2008 accrual to the Diamond Blackfan anemia arm was closed by the DSMB for lack of accrual
The Primary endpoint is hematologic response at 3 months Secondary endpoints include transfusion dependence overall survival life threatening toxicity transformation-free survival and response duration
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 00-H-0029 | OTHER | NIH NHLBI | None |