Combination Therapy of Severe Aplastic Anemia

Severe Aplastic Anemia Clinical Trial

Official title:

Treatment of Severe Aplastic Anemia With Combined Immunosuppression: Antithymocyte Globulin (ATG) and Cyclosporine A (CSA), and Mycophenolate Mofetil (MMF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001964
• Other study ID #: 000032
• Secondary ID: 00-H-0032
• Status: Completed
• Phase: Phase 2
• Start date: March 17, 2000
• Est. completion date: May 12, 2015

Study information

• Verified date: March 2021
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will test the safety and effectiveness of a combination of three drugs in treating severe aplastic anemia and preventing its recurrence. Two drugs used in this trial ATG and cyclosporine are standard combination therapy for aplastic anemia. This study will try to improve this therapy in three ways: 1) by altering the drug regimen to allow the drugs to work better; 2) by reducing the risk of kidney damage; and 3) by adding a third drug mycophenolate mofetil to try to prevent disease relapse.

Patients with severe aplastic anemia who do not have a suitable bone marrow donor or who decline bone marrow transplantation may participate in this study. Patients will have a skin test for ATG allergy, chest X-ray, blood test, and bone marrow aspiration before treatment begins. ATG will then be started, infused through a vein continuously for 4 days. Ten days after ATG is stopped, cyclosporine treatment will begin, taken twice a day by mouth in either liquid or capsule form and will continue for 6 months. Also, in the first 2 weeks of treatment, patients will be given a full dose of corticosteroid (prednisone) to prevent serum sickness that could develop as a side effect of ATG therapy. The dosage will be decreased after that. Mycophenolate will be started at the same time as ATG, in two daily doses by mouth, and will continue for 18 months.

Patients will be hospitalized at the beginning of the study. During this time, blood will be drawn at 3-week intervals and a bone marrow examination will be repeated 3 months after treatment has begun. Additional tests, including X-rays may be required. After hospital discharge, patients will be followed on an outpatient basis at 3-month intervals. The patients own physician will perform blood tests weekly and kidney and liver function tests every 2 weeks during cyclosporine therapy. Transfusions may be required initially.

Description:

Severe acquired aplastic anemia (SAA) has a poor prognosis if untreated. Bone marrow transplantation is available to only a minority of patients due to lack of a matched sibling donor, advanced age of the patient, or cost. Clinical studies at NIH and elsewhere have demonstrated excellent response rates and improved survival with immunosuppressive treatments. Laboratory data implicate underlying cytotoxic T-lymphocyte-mediated suppression of hematopoiesis as the likely proximal cause of disease in most patients. In earlier clinical protocols we treated SAA with cyclosporine A (CSA) (86-H-0007), antithymocyte globulin (ATG) (87-H-0124), and combined ATG and CSA (90-H-0146). While intensive immunosuppression is most effective, relapse is common and some patients also develop second hematologic complications like myelodysplasia. In this protocol, we modify our regimen by delaying the introduction of cyclosporine to promote ATG tolerizing effects and adding mycophenolate mofetil (MMF), a new agent that, like ATG may be relatively specific for activated lymphocytes, in an effort to reduce the high relapse rate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: May 12, 2015
• Est. primary completion date: December 9, 2003
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 99 Years

Eligibility

• INCLUSION CRITERIA:

Only patients with SAA will be admitted, defined as:

Bone marrow cellularity less than 30%.

At least two of the following blood count findings: absolute granulocyte count less than 500/mm(3); platelet count less than 20,000/mm(3); reticulocyte count less than 60,000/mm(3).

Age greater than or equal to 1 years.

Weight greater than 12 kg.

EXCLUSION CRITERIA:

Serum creatinine greater than 2 mg/dl or estimated creatinine clearance less than 40 ml/min.

Underlying carcinoma, recent history of radiation or chemotherapy.

Current pregnancy or unwillingness to be treated with oral contraceptives.

Inability to comprehend the investigational nature of the study.

Moribund status or concurrent hepatic, renal, cardiac, neurologic, or metabolic disease of such severity that death within 7 to 10 days is likely.

Evidence of other etiology than AA for bone marrow failure, including positive clastogenic stress cytogenetic assay for Fanconi anemia and marrow chromosome abnormalities typical of myelodysplasia.

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Severe Aplastic Anemia

Intervention

Drug:
• Cyclosporine A
Cyclosporine A
• ATG
ATG
• MMF
MMF

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

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

Country where clinical trial is conducted

United States, 

References & Publications (3)

Nimer SD, Ireland P, Meshkinpour A, Frane M. An increased HLA DR2 frequency is seen in aplastic anemia patients. Blood. 1994 Aug 1;84(3):923-7. — View Citation

Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. Review. — View Citation

Young NS. Acquired aplastic anemia. JAMA. 1999 Jul 21;282(3):271-8. Review. Erratum in: JAMA 2000 Jan 5;283(1):57. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	reduction in 24-month relapse	reduction in 24-month relapse	24 months

External Links

•   NIH Clinical Center Detailed Web Page