Protocol Number: 03-H-0249

Title:

A Randomized Trial of Rabbit ATG/CsA vs Campath-1H in Aplastic Anemia Patients with Refractory Pancytopenia or Suboptimal Hematologic Response After h-ATG/CsA Treatment

Number:

03-H-0249

Summary:

This study will compare two new treatments for people with severe aplastic anemia, a potentially fatal disease in which patients do not produce normal numbers of blood cells. Because they have too few red cells, patients may tire easily, have chest pains, and be short of breath even at rest. Too few white cells leave patients vulnerable to serious infections and possibly death. Too few platelets cause abnormal bleeding and easy bruising. Bleeding in the brain (stroke) can be fatal. Standard treatment with horse antithymocyte globulin (h-ATG), cyclosporine (CsA), and corticosteroids is effective, but patients often relapse. The treatments to be evaluated in this study are: 1) rabbit ATG (r-ATG) plus CsA plus corticosteroids; and 2) Campath-1H.

r-ATG is made by injecting rabbits with white blood cells. The rabbit's immune system makes antibodies to destroy the foreign white cells. The antibodies are collected and purified to make r-ATG. CsA is commonly used to prevent rejection of donated tissue after bone marrow or organ transplantation and, in combination with h-ATG, for treating aplastic anemia. Corticosteroids suppress the immune system and are given to prevent or reduce the symptoms of serum sickness, which can develop in response to the rabbit proteins in the r-ATG. Campath-1H is a laboratory-made antibody currently used to treat chronic lymphocytic leukemia. It destroys white blood cells called lymphocytes that, in aplastic anemia, are responsible for destruction of bone marrow stem cells.

Patients 15 years of age and older with severe aplastic anemia may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests, and bone marrow biopsy.

Participants are randomly assigned to one of two treatment groups: 1) r-ATG, CsA, and steroids, or 2) Campath-1H. For both treatments, it is suggested that a central venous line (large plastic tube) be placed in a large vein in the neck or chest. This tube can stay in the body and be used the entire treatment period to deliver the study drug and other medications, transfuse blood, and withdraw blood samples. Group 1 patients receive r-ATG by vein for 5 days, CsA by mouth as a liquid or capsule for 6 months, and a full dose of steroids by mouth for at least 2 weeks. After 2 weeks, when the risk of serum sickness-a reaction to the r-ATG-declines, the steroid dose is decreased. Group 2 patients receive Campath-1H by vein for 10 days. Because this drug suppresses the immune system, patients also take medicines to prevent herpes virus infection and Pneumocystis carinii-a type of pneumonia-and to treat cytomegalovirus infection, if it develops.

All patients are hospitalized for the initial testing and treatment (about 2 weeks) when the risk of infection and seizures is highest. In addition to drug treatment, patients undergo the following procedures:

- Blood tests: Throughout the hospital admission, blood samples are drawn daily to check drug side effects and the response to treatment. Samples are drawn less frequently for later tests.

- Bone marrow examination: A bone marrow sample is collected before beginning treatment, at 6 months, and then yearly. For this test, the area above the hip bone is numbed with a local anesthetic and a small sample of bone and marrow is withdrawn through a needle.

- Chest x-ray may be done upon admission.

- Other blood tests and x-rays may be required to evaluate and treat symptoms that may develop.

- Follow-up: Blood tests are done weekly by the patient's private doctor, and patients return to NIH for examinations at 3-month intervals.

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:

Bone marrow cellularity less than 30% (excluding lymphocytes)

At least two of the following:

Absolute neutrophil count less than 500/uL;

Platelet count less than 20,000/ uL;

Reticulocyte count less than 60,000/ uL.

Severe aplastic anemia refractory to prior course(s) of h-ATG/CsA defined after 3 months from treatment with lless or equal to 16 months from receiving h-ATG.

OR

Suboptimal response to initial immunosuppression with h-ATG/CsA as defined by platelet and reticulocyte count less than 50,000 /uL at 3 months.

Age greater than or equal to 15

EXCLUSION CRITERIA:

Serum creatinine greater than 2.5 mg/dL.

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

Current pregnancy or lactation or unwillingness to take contraceptives.

Diagnosis of Fanconi anemia or other congenital bone marrow failure syndromes.

Evidence of a clonal disorder on cytogenetics.

Previous hypersensitivity to Campath-1H or its components.

Prior treatment with rabbit ATG, cyclophosphamide or a comparable agent.

Underlying immunodeficiency state including seropositivity for HIV.

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

Moribound 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.

ECOG performance status greater than 2.

Special Instructions: Currently Not Provided

Keywords:

Alemtuzumab (Campath-1H)

Rabbit ATG

Severe Aplastic Anemia

Cyclosporine

Thrombocytopenia

Leukopenia

Neutropenia

Recruitment Keywords:

Severe Aplastic Anemia

Conditions:

Aplastic Anemia

Investigational Drug(s):

Alemtuzumab (Campath-1H)

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:

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

Mathe G, Amiel JL, Schwarzenberg L, Choay J, Trolard P, Schneider M, Hayat M, Schlumberger JR, Jasmin C. Bone marrow graft in man after conditioning by antilymphocytic serum. Br Med J. 1970 Apr 18;2(702):131-6. No abstract available. PMID: 4909449

Stein RS, Means RT Jr, Krantz SB, Flexner JM, Greer JP. Treatment of aplastic anemia with an investigational antilymphocyte serum prepared in rabbits. Am J Med Sci. 1994 Dec;308(6):338-43. PMID: 7985721

• 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