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Severe Aplastic Anemia, Refractory | Alemtuzumab to Treat Severe Aplastic Anemia

Severe Aplastic Anemia, Refractory research study

What is the primary objective of this study?

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 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 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.

Who is eligible to participate?

- 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 /microL Age greater than or equal to 2 years old and greater than 12 kg Prospective subjects or their parent(s)/responsible guardian(s) must be able to comprehend and be willing to sign an informed consent. EXCLUSION CRITERIA: Known Diagnosis of Fanconi's anemia Evidence of a clonal disorder on cytogenetics. In the refractory disease setting, prospective subjects with super severe neutropenia (ANC less than 200 /microL) 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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Severe Aplastic Anemia, Refractory

Severe Aplastic Anemia, Relapse

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Biological:Alemtuzumab (Campath )Campath administered at a dose of 10/mg/day for 10 days

Drug:CyclosporineSubjects who relapse after initial response to alemtuzumab therapy will have cyclosporine added to the regimen after the 6 month visit. Dosing will be based on ideal body weight and will be adjusted to maintain a target level of 200 - 400 ng /ml.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

1Subjects diagnosed with relapsed severe aplastic anemia

2Subjects diagnosed with refractory severe aplastic anemia

RelapseSubjects who relapse after initial response to alemtuzumab therapy will have cyclosporine added to the regimen after the 6 month visit.

Study Status

Active, not recruiting

Start Date: September 15, 2005

Completed Date: October 16, 2018

Phase: Phase 2

Type: Interventional

Design:

Primary Outcome: The primary endpoint for either trial (relapsed SAA or refractory SAA) will be the response rate at 6 months.

Secondary Outcome: Robustness of hematologic recovery with reticulocyte or platelet count = 50,000/microliter

Study sponsors, principal investigator, and references

Principal Investigator: Neal S Young, M.D.

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

Collaborator:

More information:https://clinicaltrials.gov/show/NCT00195624

Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. Review.

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