Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00195624
Status:
COMPLETED
Last Update Posted:
2020-07-07
First Post:
2005-09-16
Brief Title:
Alemtuzumab to Treat Severe Aplastic Anemia
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 Campath in Patients With Relapsed or Refractory Severe Aplastic Anemia
Status:
COMPLETED
Status Verified Date:
2018-10
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 usefulness of a new immunosuppressive drug alemtuzumab Campath in patients with severe aplastic anemia SAA SAA is a rare and serious blood disorder in which the bone marrow stops making red blood cells white blood cells and platelets Alemtuzumab is a monoclonal antibody that attaches to and kills white blood cells called lymphocytes In certain types of aplastic anemia lymphocytes are responsible for the destruction of stem cells in the bone marrow leading to a decrease in blood counts Because alemtuzumab destroys lymphocytes it may be effective in treating aplastic anemia Alemtuzumab is currently approved to treat chronic lymphocytic leukemia and is also helpful in other conditions that require immunosuppression such as rheumatoid arthritis and immune cytopenias
Patients 2 years of age and older with severe aplastic anemia whose disease does not respond to immunosuppressive therapy or has recurred following immunosuppressive therapy may be eligible for this study Participants undergo the following tests and procedures
Pretreatment evaluation Patients have a medical history physical examination blood tests electrocardiogram EKG echocardiogram 24-hour Holter monitor continuous 24-hour monitoring of electrical activity of the heart bone marrow biopsy withdrawal through a needle of a small sample of bone marrow for analysis
Placement of a central line if needed An intravenous line tube is placed into a major vein in the patients chest It can stay in the body for the entire treatment period and be used to give chemotherapy or other medications including antibiotics and blood transfusions if needed and to withdraw blood samples
Alemtuzumab therapy Patients are admitted to the NIH Clinical Center for the first few injections for close monitoring of side effects After receiving an initial small test dose patients begin the first of ten daily injections under the skin each lasting about 2 hours Once patients tolerate the infusions with minimal or no side effects they may be given the remaining infusions on an outpatient basis Patients who relapse after their initial response to alemtuzumab are given cyclosporine to see if this drug will boost their immune response
Patients receive transfusions growth factors and antibiotic therapy as needed
Infection therapy Patients are given aerosolized pentamidine to protect against lung infections and valacyclovir to protect against herpes infections
A blood test is done and vital signs are measured every day while patients receive alemtuzumab
Patients have an echocardiogram and 24-hour Holter monitor after the last dose of alemtuzumab
Blood tests are done weekly for the first 3 months after alemtuzumab administration then every other week until 6 months
Patients return to the NIH for follow-up visits 1 month 3 months 6 months and yearly for 5 years after the last dose of alemtuzumab for the following tests and evaluations
Blood test
Repeat echocardiogram at 3-month visit
Repeat bone marrow biopsy 6 months and 12 months after alemtuzumab then as clinically indicated for 5 years
Patients 2 years of age and older with severe aplastic anemia whose disease does not respond to immunosuppressive therapy or has recurred following immunosuppressive therapy may be eligible for this study Participants undergo the following tests and procedures
Pretreatment evaluation Patients have a medical history physical examination blood tests electrocardiogram EKG echocardiogram 24-hour Holter monitor continuous 24-hour monitoring of electrical activity of the heart bone marrow biopsy withdrawal through a needle of a small sample of bone marrow for analysis
Placement of a central line if needed An intravenous line tube is placed into a major vein in the patients chest It can stay in the body for the entire treatment period and be used to give chemotherapy or other medications including antibiotics and blood transfusions if needed and to withdraw blood samples
Alemtuzumab therapy Patients are admitted to the NIH Clinical Center for the first few injections for close monitoring of side effects After receiving an initial small test dose patients begin the first of ten daily injections under the skin each lasting about 2 hours Once patients tolerate the infusions with minimal or no side effects they may be given the remaining infusions on an outpatient basis Patients who relapse after their initial response to alemtuzumab are given cyclosporine to see if this drug will boost their immune response
Patients receive transfusions growth factors and antibiotic therapy as needed
Infection therapy Patients are given aerosolized pentamidine to protect against lung infections and valacyclovir to protect against herpes infections
A blood test is done and vital signs are measured every day while patients receive alemtuzumab
Patients have an echocardiogram and 24-hour Holter monitor after the last dose of alemtuzumab
Blood tests are done weekly for the first 3 months after alemtuzumab administration then every other week until 6 months
Patients return to the NIH for follow-up visits 1 month 3 months 6 months and yearly for 5 years after the last dose of alemtuzumab for the following tests and evaluations
Blood test
Repeat echocardiogram at 3-month visit
Repeat bone marrow biopsy 6 months and 12 months after alemtuzumab then as clinically indicated for 5 years
Detailed Description:
Hematopoietic stem cell destruction in many human bone marrow failure syndromes is now recognized to be secondary to immune mechanisms Severe aplastic anemia SAA is a life-threatening blood disease which can be effectively treated with immunosuppressive drug regimens However a significant minority of patients with SAA fail to respond to a single course of horse antithymocyte globulin and cyclosporine and other patients experience relapse especially on discontinuation of therapy Pancytopenia secondary to refractory or relapsed aplastic anemia has a poor prognosis with death usually resulting from infectious complications Alemtuzumab Campath is a humanized IgG1 monoclonal antibody directed against the CD52 protein CD52 is expressed on all lymphocytes and monocytes Alemtuzumab Campath produces profound and persistent lymphopenia The antibody has been used to treat a wide range of autoimmune diseases lymphoid malignancies and in solid organ and hematopoietic stem cell transplantation In our limited experience with alemtuzumab for the treatment of SAA refractory to horse antithymocyte globulin meaningful hematologic responses have been observed and toxicity has been modest
We therefore propose a non-randomized pilot phase II study of this humanized monoclonal antibody in SAA relapsed or refractory to ATG Commercially available alemtuzumab Campath will be administered at 10 mg per day subcutaneously for 10 days total
The primary end point of the study is the response rate at 6 months defined as no longer satisfying blood count criteria for SAA
Relapse robustness of the hematopoietic recovery at 3 and 6 months 3 months responses survival and clonal evolution to myelodysplasia and acute leukemia will be secondary end points
We therefore propose a non-randomized pilot phase II study of this humanized monoclonal antibody in SAA relapsed or refractory to ATG Commercially available alemtuzumab Campath will be administered at 10 mg per day subcutaneously for 10 days total
The primary end point of the study is the response rate at 6 months defined as no longer satisfying blood count criteria for SAA
Relapse robustness of the hematopoietic recovery at 3 and 6 months 3 months responses survival and clonal evolution to myelodysplasia and acute leukemia will be secondary end points
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-0242 | None | None | None |