Protocol Number: 03-H-0193

Title:

A Randomized Trial of a Novel Immunosuppressive Combination of ATG, CsA, and Sirolimus (Rapamune® (Registered Trademark)) vs a Slow Taper Cyclosporine Regimen in Subjects with Severe Aplastic Anemia

Number:

03-H-0193

Summary:

Immunosuppressive treatment (administering drugs that suppress the immune system) is often successful for people with severe aplastic anemia (SAA). However, SAA patients tend to be highly susceptible to relapse, even after successful immunosuppressive treatment. Research suggests that SAA is an autoimmune disease and thus may require longer immunosuppressive treatment with different drugs.

The purpose of this study is to compare two immunosuppressive regimens with the goal of decreasing relapse in SAA patients.

Study participants will be placed in one of two study groups. One group will receive a combined drug treatment of antithymocyte globulin (ATG), cyclosporine (CsA) and sirolimus for six months. The other group will receive a combined treatment of ATG and CsA for 6 months, followed by a slow taper of CsA over the next 18 months.

Upon admission to NIH, patients will undergo several days of preliminary testing and receive the medications; they will be hospitalized during this period (7-10 days). Study participants will have blood drawn periodically during treatment.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Severe aplastic anemia confirmed at NIH by:

a.. Bone marrow cellularity less than 30% (excluding lymphocytes)

b.. At least two of the following: Absolute neutrophil count less than 500/ uL; Platelet count less than 20,000/ uL; Absolute reticulocyte count less than 60,000/ uL

Age greater than or equal to 2 years old

Weight greater than 12 kg

EXCLUSION CRITERIA:

Serum creatinine greater than 2.5 mg/dL

Underlying carcinoma (except local cervical, basal cell, squamous cell)

Prior immunosuppressive therapy with ATG, ALG, or cyclophospamide.

Current pregnancy or lactation or unwillingness to take oral contraceptives or use an effective method of birth control.

Diagnosis of Fanconi anemia or other congenital bone marrow failure syndromes

Evidence of a clonal disorder on cytogenetics

Underlying immunodeficiency state including seropositivity for HIV

Inability to understand the investigational nature of the study or give informed consent

ECOG performance status greater than 2

Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patients ability to tolerate protocol therapy, or that death within 7-10 days is likely.

Special Instructions: Currently Not Provided

Keywords:

Bone Marrow Failure

Cyclosporine

Anti Thymocyte Globulin

Recruitment Keywords:

Severe Aplastic Anemia

Conditions:

Aplastic Anemia

Investigational Drug(s):

Sirolimus (Rapamune)

Investigational Device(s):

None

Contacts:

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

Citations:

Bacigalupo A, Brand R, Oneto R, Bruno B, Socie G, Passweg J, Locasciulli A, Van Lint MT, Tichelli A, McCann S, Marsh J, Ljungman P, Hows J, Marin P, Schrezenmeier H. Treatment of acquired severe aplastic anemia: bone marrow transplantation

compared with immunosuppressive therapy--The European Group for Blood and Marrow Transplantation experience.

Semin Hematol. 2000 Jan;37(1):69-80. Review. PMID: 10676912

Young NS. Acquired aplastic anemia. Ann Intern Med. 2002 Apr 2;136(7):534-46. Review. PMID: 11926789

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. PMID: 9134878

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

Warren Grant Magnuson Clinical Center (CC)
National Institutes of Health (NIH)
Bethesda, Maryland 20892. Last update: 10/16/2004