Protocol Number: 09-H-0183

Title:

Horse ATG/CsA in Aplastic Anemia Patients Unresponsive to or with a Suboptimal Response to Rabbit ATG/CsA Treatment

Number:

09-H-0183

Summary:

Background:

- Severe plastic anemia can lead to problems with bone marrow platelet production and result in low blood platelet counts, which require frequent platelet transfusions to improve blood clotting.

- A standard treatment for SAA involves injections of rabbit-antithymocyte globulin (r-ATG). r-ATG is developed by injecting horses with a type of human white blood cells called thymocytes. The horse's immune system reacts against these cells and makes antibodies that can destroy them. These antibodies are collected and purified to make r-ATG. Horses can also be used for this procedure to make horse-antithymocyte globulin (h-ATG).

- h-ATG is approved by the Food and Drug Administration for the treatment of aplastic anemia. h-ATG is a standard first-line method to treat aplastic anemia, but researchers do not know how effective it is in patients who were first treated unsuccessfully with r-ATG.

Objectives:

- To evaluate the effectiveness and safety of horse-ATG (with cyclosporine) in increasing blood counts and reducing the need for transfusions in aplastic anemia patients who have failed to respond to prior immunosuppressive treatment with rabbit-ATG and cyclosporine.

Eligibility:

- Patients 2 years of age and older who have consistently low blood platelet counts related to aplastic anemia that has not responded to conventional treatment with rabbit-ATG.

Design:

- After initial screening, medical history, and blood tests, patients will be admitted to the inpatient unit at the National Institutes of Health Clinical Center. Researchers will perform a skin test with h-ATG to check for allergic or other adverse reaction.

- After the skin test, h-ATG will be given into a vein continuously over 4 days.

- Cyclosporine will also be given to improve the response rate of ATG treatment. Treatment with cyclosporine will start the same day as the h-ATG, either in liquid or capsule form, and continued for 6 months. The dose of cyclosporine will be monitored and adjusted based on blood levels and signs of side effects in the kidney and liver.

- To prevent or treat infections that may result from cyclosporine's effect on the immune system, patients will also take inhaled or capsule doses of pentamidine.

- After the study is completed, patients will have followup evaluations every 3 months, 6 months, and annually for 5 years. Evaluations will include blood samples and periodic bone marrow biopsies.

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:

The study will be open to all subjects who satisfy the inclusion criteria and provide an informed consent to the protocol. No subjects will be excluded from participation based on gender, race or ethnicity.

Epidemiologic studies suggest that an estimated 2-4 cases per million of aplastic anemia will be diagnosed each year worldwide; the incidence occurs in three peaks: 2-5 years, 20-25 years and 55-60 years; cases are approximately evenly split between male and females. Based on previous experience at our institution, approximately 40-50 new patients with aplastic anemia per year will be evaluated for protocol participation and the distribution in this patient population will be: gender: 60% males and 40% females; race/ethnicity: approximately 55% White, 15% Black, 6% Asian and 24% Hispanic; age: will range between 2 and 82 (median age of 30), and that 15% of patients will be under the age of 18.

Women of childbearing potential must agree to use adequate contraception prior to (hormonal or barrier method of birth control; abstinence) and for the duration of study participation.

EXCLUSION CRITERIA:

For pregnant and nursing mothers:

H-ATG: (Pregnancy category C) Animal reproduction studies have not been conducted with ATGAM and it is not known whether ATGAM can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. It is also not known whether this drug is excreted in human milk. Therefore pregnant women will be excluded from participation on this study.

CsA: (Pregnancy Category C) Animal studies have shown reproductive toxicity in rats and rabbits. There are no adequate and well-controlled studies in pregnant women; therefore, pregnant women will be excluded from participation on this study.

Special Instructions:

Currently Not Provided

Keywords:

h-ATG

Anti -Thymocyte Globulin

Lymphocyte Immune Globulin

Recruitment Keyword(s):

Aplastic Anemia

Condition(s):

Anemia, Aplastic

Anemia, Hypoplastic

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: h-ATG (ATGAM(Registered Trademark))

Drug: Cyclosporine (Gengraf(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, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006 Oct 15;108(8):2509-19.

Maciejewski JP, Selleri C, Sato T, Anderson S, Young NS. Increased expression of Fas antigen on bone marrow CD34+ cells of patients with aplastic anaemia. Br J Haematol. 1995 Sep;91(1):245-52.

Risitano AM, Maciejewski JP, Green S, Plasilova M, Zeng W, Young NS. In-vivo dominant immune responses in aplastic anaemia: molecular tracking of putatively pathogenetic T-cell clones by TCR beta-CDR3 sequencing. Lancet. 2004 Jul 24-30;364(9431):355-64.

• 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 Clinical Research Informatics, CC.

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

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 11/25/2009