This site became the new on June 19th. Learn more.
Show more Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu
Give us feedback

Combination Therapy of Severe Aplastic Anemia

This study has been completed.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ) Identifier:
First received: January 18, 2000
Last updated: June 30, 2017
Last verified: April 26, 2017

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.

Condition Intervention Phase
Severe Aplastic Anemia Drug: Cyclosporine Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Severe Aplastic Anemia With Combined Immunosuppression: Antithymocyte Globulin (ATG) and Cyclosporine A (CSA), and Mycophenolate Mofetil (MMF)

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):

Primary Outcome Measures:
  • Disease Response. [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • Toxicity, survival. [ Time Frame: Months/years ]

Enrollment: 104
Study Start Date: December 1, 1999
Study Completion Date: May 12, 2015
Primary Completion Date: December 9, 2003 (Final data collection date for primary outcome measure)
Detailed 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.

Ages Eligible for Study:   1 Year to 99 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.


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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00001964

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Neal S Young, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI) Identifier: NCT00001964     History of Changes
Other Study ID Numbers: 000032
Study First Received: January 18, 2000
Last Updated: June 30, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Bone Marrow Failure
Aplastic Anemia

Additional relevant MeSH terms:
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors processed this record on September 21, 2017