Official Title: “A Pilot Study of Alemtuzumab (Campath) in Patients With Relapsed or Refractory Severe Aplastic Anemia”

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...

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: Alemtuzumab (Campath® (Registered Trademark))
  • N/A

Primary Measures

• Response rate at six months, defined as no longer satisfying blood count criteria for SAA.

Secondary Measures

• Relapse, robustness of the hematopoietic recovery at three and six months, three months responses, survival, and clonal evolution to myelodysplasia and acute leukemia.

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 2 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Overall Clinical Trial Officials and Contacts

Overall Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00195624

Study ID Number: 050242

ClinicalTrials.gov Identifier: NCT00195624

Health Authority: United States: Federal Government

NIH Clinical Center Detailed Web Page