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

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Cyclosporine; Cyclosporins

Criteria

• All patients 2 years old or over with SAA who have failed initial immunosuppression with r-ATG/CsA and are not candidates for a matched sibling marrow transplantation will be considered for enrollment. Patients who have a suitable matched sibling donor will be referred for consideration of allogeneic bone marrow transplantation. Patients not willing to undergo transplantation will be considered for enrollment. Eligibility will be determined on another screening Hematology Branch protocol (97-H-0041) or another active Hematology branch protocol. The time between determination of eligibility and signing consent to participate on this protocol and initiate treatment on this protocol will not exceed 90 days.

INCLUSION CRITERIA:

1. Diagnosed with SAA characterized by:

1. Bone marrow cellularity < 30% (excluding lymphocytes)

2. At least two of the following:

i. Absolute neutrophil count <500/ microL

ii. Platelet count <20,000/ microL

iii. Reticulocyte count <60,000/ microL

2. Failure to respond to an initial course of r-ATG/CsA or cyclophosphamide at least 3 months post-treatment or a suboptimal response to initial therapy defined by both platelet and reticulocyte count < 50,000 /microL at 3 months post-treatment

3. Age greater than or equal to 2 years of age

EXCLUSION CRITERIA:

1. Diagnosis of Fanconi anemia. Patients with very severe neutropenia (ANC < 200 /microL) will not be excluded initially if results of Fanconi anemia testing are not available or pending. If evidence of Fanconi anemia is later identified, the subject will go off study.

2. Evidence of a clonal disorder on cytogenetics. Patients with very severe neutropenia (ANC < 200/uL) will not be excluded initially if results of cytogenetics are not available or pending. If evidence of a clonal disorder is later identified, the subject will go off study.

3. Patients who received prior course(s) of alemtuzumab will not be excluded.

4. Infection not adequately responding to appropriate therapy

5. HIV seropositivity

6. 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.

7. Subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible

8. Serum creatinine > 2.5 mg/dL

9. Current pregnancy, breast-feeding or unwillingness to refrain from pregnancy if of child bearing potential

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