Protocol Number: 05-H-0242

Title:

A Pilot Study of Alemtuzumab (Campath) in Patients with Relapsed or Refractory Severe Aplastic Anemia

Number:

05-H-0242

Summary:

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.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

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

Special Instructions:

Currently Not Provided

Keywords:

Immunosuppression

Campath 1-H

Pancytopenia

Monoclonal Antibody

T-Cells

Hematopoiesis

Autoimmunity

Thrombocytopenia

Neutropenia

Recruitment Keyword(s):

Severe Aplastic Anemia

SAA

Condition(s):

Relapsed or Refractory Severe Aplastic Anemia

Severe Aplastic Anemia

Investigational Drug(s):

Alemtuzumab (Campath® (Registered Trademark))

Investigational Device(s):

None

Intervention(s):

Drug: Alemtuzumab (Campath® (Registered Trademark))

Supporting Site:

National Heart, Lung and Blood Institute

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia.Blood. 1995 Jun 15;85(12):3367-77. Review. No abstract available.

Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. Review. No abstract available.

Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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