| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Relapsed or Refractory Severe Aplastic Anemia - Severe Aplastic Anemia |
| Purpose: |
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This study will evaluate the safety and usefulness of a new immunosuppressive drug,
alemtuzumab (Campath(Registered Trademark)), 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 patient's 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
infusions for close monitoring of side effects. After receiving an initial small test
dose, patients begin the first of ten daily infusions, 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.
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| Study summary: |
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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(Registered Trademark)) is a humanized IgG1 monoclonal
antibody directed against the CD52 protein; CD52 is expressed on all lymphocytes and
monocytes. Alemtuzumab (Campath(Registered Trademark)) 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(Registered Trademark)) will be administered at 10 mg per day by intravenous
infusion 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. |
| Criteria: |
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- INCLUSION CRITERIA:
Relapsed severe aplastic anemia after initial hematologic response to a prior course of
h-ATG or r-ATG based immunosuppression
Or
Refractory severe aplastic anemia not responding to both horse-ATG and rabbit ATG-based
immunosuppression
The criteria for severe aplastic anemia are two of the three criteria:
- Absolute neutrophil count less than or equal to 500 /mm(3)
- Platelets to less than or equal to 20,000/mm(3)
- Absolute reticulocyte count less than 60,000 /uL
Age greater than or equal to 2 years old
Patients or their parent(s)/responsible guardian(s) must be able to comprehend and be
willing to sign an informed consent.
EXCLUSION CRITERIA:
Diagnosis of Fanconi's anemia
Evidence of a clonal disorder on cytogenetics. In the refractory disease setting,
patients with super severe neutropenia (ANC less than 200 /uL) will not be excluded if
results of cytogenetics are not available or pending.
Infection not adequately responding to appropriate therapy
HIV positivity
Failure to discontinue the herbal supplements Echinacea purpurea or Usnea barbata (Old
Man's Beard) within 2 weeks of enrollment
Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious,
or metabolic disease of such severity that it would preclude the patient's ability to
tolerate protocol therapy, or that death within 7-10 days is likely
Previous hypersensitivity to alemtuzumab or its components
Potential subjects with cancer who are on active chemotherapeutic treatment or who take
drugs with hematological effects will not be eligible
Current pregnancy, or unwilling to take oral contraceptives or refrain from pregnancy if
of childbearing potential
Not able to understand the investigational nature of the study or give informed consent |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
Patient Recruitment and Public Liaison Office
Email: prpl@mail.cc.nih.gov
Phone: (800) 411-1222 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 21, 2011 |
Modifications to
this listing: |
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above to view all information about this clinical trial. |
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