Ignite Creation Date:
2024-05-05 @ 12:02 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00217594
Status:
COMPLETED
Last Update Posted:
2018-10-30
First Post:
2005-09-20
Brief Title:
A Pilot Study of Alemtuzumab CampathR in Patients With Myelodysplastic Syndrome
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Study of Alemtuzumab CampathR in Patients With Myelodysplastic Syndrome MDS
Status:
COMPLETED
Status Verified Date:
2017-10-17
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 the safety and effectiveness of a genetically engineered antibody alemtuzumab CampathR on patients with myelodysplastic syndrome MDS is made up of malignant stem cell disorders that can mean low levels of red blood cells-that is anemia-and low counts of white blood cells and platelets Patients with MDS are at risk for infection spontaneous bleeding and possible progression to leukemia a cancer of bone marrow Although bone marrow can produce some blood cells patients with MDS experience a decrease in production of blood cells Alemtuzumab recognizes specific types of white cells called lymphocytes and destroys them This study will examine not only the usefulness of the medication but also the side effects in patients with MDS
Patients ages 18 to 72 who have MDS that requires transfusions and who do not have HIV or a life expectancy of less than 6 months may be eligible for this study Screening tests include a complete physical examination and medical history There will be a collection of about 8 tablespoons of blood for analysis of blood counts as well as liver kidney and thyroid function a pregnancy test an electrocardiogram EKG to measure electrical activity of the heartbeat an echocardiogram ECHO which uses sound waves to evaluate heart function wearing of a Holter monitor for 24 hours while the electrical activity of the heart is recorded and a bone marrow biopsy Patients should not receive any vaccines when taking alemtuzumab or for at least 12 months after the last dose In addition patients should not take the herbal supplements Echinacea purpurea or Usnea 2 weeks before beginning the study and during it
For the study all patients will receive a test dose of 1 mg of alemtuzumab infused into a vein during the course of 1 hour If the dose is tolerated the medication will be given at 10 mg doses into the vein for 10 days as an infusion of 2 hours Blood samples of 2 tablespoons will be taken daily and vital signs will be measured daily The ECHO and 24-hour Holter monitoring will be repeated after patients receive the last dose of the medication Because suppression of the immune system results from a decrease in white cells that fight infections patients will take medications to protect them against infections and to treat them if infections occur If needed patients will receive blood transfusions for their MDS Side effects of alemtuzumab involve a temporarily significant lowering of the number of red blood cells white cells and platelets Side effects of the infusion can be rigidity or stiffness and fever as well as risks of infections resulting from the decrease of white blood cells Blood counts and reactions to all procedures will be carefully monitored throughout the study After patients receive the last dose of alemtuzumab they will have follow-up by their referring doctor or at NIH They must be able to return to NIH after 1 month 3 months 6 months and annually for 5 years after the study At follow-up visits there will be blood tests to reevaluate blood counts and test for the presence of viruses Blood tests will be done weekly for the first 3 months after patients have completed taking alemtuzumab every other week until 6 months and then annually for 5 years There will also be a repeat ECHO at the 3-month visit and a repeat bone marrow biopsy at the 5-month and 12-month follow-up visits and as needed after that
This study may or may not have a direct benefit for participants For some the antibody may improve blood counts and decrease the need for transfusions Knowledge gained in the study may help people in the future
Patients ages 18 to 72 who have MDS that requires transfusions and who do not have HIV or a life expectancy of less than 6 months may be eligible for this study Screening tests include a complete physical examination and medical history There will be a collection of about 8 tablespoons of blood for analysis of blood counts as well as liver kidney and thyroid function a pregnancy test an electrocardiogram EKG to measure electrical activity of the heartbeat an echocardiogram ECHO which uses sound waves to evaluate heart function wearing of a Holter monitor for 24 hours while the electrical activity of the heart is recorded and a bone marrow biopsy Patients should not receive any vaccines when taking alemtuzumab or for at least 12 months after the last dose In addition patients should not take the herbal supplements Echinacea purpurea or Usnea 2 weeks before beginning the study and during it
For the study all patients will receive a test dose of 1 mg of alemtuzumab infused into a vein during the course of 1 hour If the dose is tolerated the medication will be given at 10 mg doses into the vein for 10 days as an infusion of 2 hours Blood samples of 2 tablespoons will be taken daily and vital signs will be measured daily The ECHO and 24-hour Holter monitoring will be repeated after patients receive the last dose of the medication Because suppression of the immune system results from a decrease in white cells that fight infections patients will take medications to protect them against infections and to treat them if infections occur If needed patients will receive blood transfusions for their MDS Side effects of alemtuzumab involve a temporarily significant lowering of the number of red blood cells white cells and platelets Side effects of the infusion can be rigidity or stiffness and fever as well as risks of infections resulting from the decrease of white blood cells Blood counts and reactions to all procedures will be carefully monitored throughout the study After patients receive the last dose of alemtuzumab they will have follow-up by their referring doctor or at NIH They must be able to return to NIH after 1 month 3 months 6 months and annually for 5 years after the study At follow-up visits there will be blood tests to reevaluate blood counts and test for the presence of viruses Blood tests will be done weekly for the first 3 months after patients have completed taking alemtuzumab every other week until 6 months and then annually for 5 years There will also be a repeat ECHO at the 3-month visit and a repeat bone marrow biopsy at the 5-month and 12-month follow-up visits and as needed after that
This study may or may not have a direct benefit for participants For some the antibody may improve blood counts and decrease the need for transfusions Knowledge gained in the study may help people in the future
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 leukopenia 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 horse antithymocyte globulin h-ATG However non-response 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 h-ATGCsA non-responders 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 alemtuzumab CampathR is a humanized IgG1 monoclonal antibody directed against the CD52 protein which is highly expressed on all lymphoid cells and monocytes Alemtuzumab CampathR produces profound and persistent lymphopenia affecting predominantly the CD4 T cell subset This property has made it attractive in the treatment of a wide range of diseases including rheumatoid arthritis multiple sclerosis ocular inflammatory disease lymphoid malignancies organ allograft rejection and in conditioning regimens in stem cell transplantation to prevent graft failure and graft-versus-host disease
We therefore propose a non-randomized off label pilot Phase III study of alemtuzumab Campath in MDS patients who are likely to respond to immunosuppression
Primary endpoints will be changes in peripheral blood counts platelets absolute neutrophil count reticulocyte count hemoglobin Secondary endpoints in transfusion-dependent patients include improvement in the transfusion requirements measured as decrease in the number of transfusion administered on as needed basis duration of response late effects of treatment relapse and survival
One such novel therapy alemtuzumab CampathR is a humanized IgG1 monoclonal antibody directed against the CD52 protein which is highly expressed on all lymphoid cells and monocytes Alemtuzumab CampathR produces profound and persistent lymphopenia affecting predominantly the CD4 T cell subset This property has made it attractive in the treatment of a wide range of diseases including rheumatoid arthritis multiple sclerosis ocular inflammatory disease lymphoid malignancies organ allograft rejection and in conditioning regimens in stem cell transplantation to prevent graft failure and graft-versus-host disease
We therefore propose a non-randomized off label pilot Phase III study of alemtuzumab Campath in MDS patients who are likely to respond to immunosuppression
Primary endpoints will be changes in peripheral blood counts platelets absolute neutrophil count reticulocyte count hemoglobin Secondary endpoints in transfusion-dependent patients include improvement in the transfusion requirements measured as decrease in the number of transfusion administered on as needed basis duration of response late effects of treatment relapse and survival
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 |
|---|---|---|---|
| 05-H-0206 | None | None | None |