Ignite Creation Date:
2024-05-05 @ 11:32 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00072969
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2003-11-12
Brief Title:
A Randomized Trial of Recombinant Humanized Anti-IL-2 Receptor Antibody Daclizumab Versus Antithymocyte Globulin ATG to Treat the Cytopenia of Myelodysplastic Syndrome MDS
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Trial of Recombinant Humanized Anti-IL-2 Receptor Antibody Daclizumab Versus Antithymocyte Globulin ATG to Treat the Cytopenia of Myelodysplastic Syndrome MDS
Status:
COMPLETED
Status Verified Date:
2005-08
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:
This study will evaluate a new immunosupressive therapy Daclizumab and compare it with antithymocyte globulin ATG to treat cytopenia that is the deficiency of cellular elements of the blood in myelodysplastic syndrome MDS Daclizumab is an anti-interleukin-2 receptor IL-2 antibody MDS also known as myelodysplasia is a disorder that can cause anemia spontaneous bleeding and greater risk of infections Although the bone marrow can still produce some blood cells very few reach the bloodstream The cause of MDS is not known although its behavior is Many patients need transfusions of red blood cells They may also develop leukemia which is often quite resistant to treatment with chemotherapy However the progression of the disorder to leukemia is usually slow taking many years
Patients 18 years of age and older who have MDS may be eligible for this study Participants will undergo the following tests and procedures
Medical history and physical examination
Collection of blood for tests including blood counts liver and kidney function and antibodies against common viruses
Chest x-ray
Electrocardiogram
Bone marrow sample to confirm the diagnosis
Participants will randomly receive either ATG or Daclizumab If they are in the group to receive ATG they will be admitted as inpatients to undergo the first 10 to 14 days of treatment If they do not already have a catheter in one of the large veins of the neck chest or arm one will be placed ATG will be given through the catheter Blood counts and other blood analysis will be monitored daily while the patients are treated After about 10 days they will be released to be under the care of their referring physicians Those participants who are in the group to receive Daclizumab will receive a total of five doses one every 2 weeks over 8 weeks given through a vein as a 15-minute infusion The first third and fifth dose will be given at the outpatient clinic The second and fourth doses can be given either at the clinic or by the patients primary hematologists
All patients will be followed as outpatients at 3-month intervals for the first year and then every 6 months for the next 3 years Afterward follow-up will be yearly A small sample of blood will be drawn at the visits Also bone marrow examinations will be requested at the 6-month intervals for the first 3 years of treatment If the treatment that patients are assigned to does not work after 6 months they will be eligible to receive the other treatment-provided that they have complied with the required blood tests and visits to the clinic required to assess the patients safety
Patients 18 years of age and older who have MDS may be eligible for this study Participants will undergo the following tests and procedures
Medical history and physical examination
Collection of blood for tests including blood counts liver and kidney function and antibodies against common viruses
Chest x-ray
Electrocardiogram
Bone marrow sample to confirm the diagnosis
Participants will randomly receive either ATG or Daclizumab If they are in the group to receive ATG they will be admitted as inpatients to undergo the first 10 to 14 days of treatment If they do not already have a catheter in one of the large veins of the neck chest or arm one will be placed ATG will be given through the catheter Blood counts and other blood analysis will be monitored daily while the patients are treated After about 10 days they will be released to be under the care of their referring physicians Those participants who are in the group to receive Daclizumab will receive a total of five doses one every 2 weeks over 8 weeks given through a vein as a 15-minute infusion The first third and fifth dose will be given at the outpatient clinic The second and fourth doses can be given either at the clinic or by the patients primary hematologists
All patients will be followed as outpatients at 3-month intervals for the first year and then every 6 months for the next 3 years Afterward follow-up will be yearly A small sample of blood will be drawn at the visits Also bone marrow examinations will be requested at the 6-month intervals for the first 3 years of treatment If the treatment that patients are assigned to does not work after 6 months they will be eligible to receive the other treatment-provided that they have complied with the required blood tests and visits to the clinic required to assess the patients safety
Detailed Description:
Many bone marrow failure syndromes in humans are now recognized to result from immunological mechanisms These diseases include aplastic anemia pure red cell aplasia and some types of myelodysplasia Patients with these conditions who may suffer variable degrees of anemia leukocytopenia and thrombocytopenia alone or in combination have been shown to respond to a wide variety of immunosuppressive agents ranging from corticosteroids to cyclosporine CSA and antithymocyte globulin ATG however nonresponse and relapse continues to be a problem Why some patients do not respond initially or others respond and then relapse is unclear Autoreactive T cells may be resistant to the effect of ATGCsA nonresponders while in others residual autoreactive T cells expand post-treatment leading to hematopoietic stem cell destruction and recurrent pancytopenia relapse Therefore novel less toxic immunosuppressive regimens that increase response rates and hematologic recovery and decrease relapse rates are needed
One such novel therapy Daclizumab a humanized anti-interleukin-2 receptor lL-2R monoclonal antibody mAb acts against activated lymphocytes thus sharing an important mechanism of action with ATG The mAb is much less toxic than ATG and may be administered to outpatients at relatively infrequent intervals every 2 weeks Treatments with ATG alone and CsA alone have demonstrated varying degrees of success in alleviating the cytopenia of MDS Our experience suggests that ATG rather than CSA is the more effective agent inducing hematological responses in susceptible MDS patients and that certain variables including the patients age whether or not they were HLA DR15 and days of red cell transfusion dependence prior to treatment were predictive of response
We therefore propose this randomized phase II study to evaluate and compare a new immunosuppressive therapy Daclizumab with antithymocyte globulin ATG to treat the cytopenia of MDS in a population of subjects with intermediate or high predicted probability of response
One such novel therapy Daclizumab a humanized anti-interleukin-2 receptor lL-2R monoclonal antibody mAb acts against activated lymphocytes thus sharing an important mechanism of action with ATG The mAb is much less toxic than ATG and may be administered to outpatients at relatively infrequent intervals every 2 weeks Treatments with ATG alone and CsA alone have demonstrated varying degrees of success in alleviating the cytopenia of MDS Our experience suggests that ATG rather than CSA is the more effective agent inducing hematological responses in susceptible MDS patients and that certain variables including the patients age whether or not they were HLA DR15 and days of red cell transfusion dependence prior to treatment were predictive of response
We therefore propose this randomized phase II study to evaluate and compare a new immunosuppressive therapy Daclizumab with antithymocyte globulin ATG to treat the cytopenia of MDS in a population of subjects with intermediate or high predicted probability of response
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 |
|---|---|---|---|
| 04-H-0026 | None | None | None |