Cyclophosphamide Plus Cyclosporine in Treatment-Naive Severe Aplastic Anemia

This study has been completed.
Information provided by (Responsible Party):
Danielle Townsley, M.D., National Institutes of Health Clinical Center (CC) Identifier:
First received: August 31, 2010
Last updated: October 13, 2015
Last verified: October 2015


  • Severe aplastic anemia (SAA) can lead to problems with bone marrow health and result in low blood cell counts, which require frequent transfusions. Standard treatment for SAA involves injections of antithymocyte globulin (ATG) plus cyclosporine (CsA). This regimen has been shown to improve the blood counts in about two-thirds of patients. However, the ATG/CsA regimen has the following limitations: (a) the disease can come back (relapse) in about one-third of patients who improve initially; and (b) in about 10% to 15% of cases, certain types of bone marrow cancer (such as myelodysplasia and leukemia) can develop (called evolution). Experience with other drugs in SAA such as cyclophosphamide suggests that similar response rates to ATG/CsA can be achieved with a lower risk of relapse and clonal evolution. However, cyclophosphamide was found to have significant side effects in SAA when investigated over 10 years ago due to increase risk of fungal infections.
  • Better antibiotic drugs against fungus have been developed and are widely used to treat patients who have low white blood cell counts and are at risk of developing infections. In SAA patients in particular, these newer antibiotics have had a large impact in preventing and treating fungus infections. Researchers are revisiting the use of cyclophosphamide in SAA treatment, and plan to give a lower dose of CsA in combination with the immune-suppressing drug cyclophosphamide, as well as antibiotics to protect against infections, as a possible treatment for the disease.


- To determine the safety and effectiveness of the combination of cyclophosphamide and cyclosporine in treating severe aplastic anemia that has not been treated with immunosuppressive therapy.

Condition Intervention Phase
Aplastic Anemia
Severe Aplastic Anemia
Drug: Cyclophosphamide
Drug: Cyclosporine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cyclophosphamide Plus Cyclosporine in Treatment-Naive Severe Aplastic Anemia

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The Primary Objective is to Evaluate the Safety and Activity Profile of Cyclophosphamide and Cyclosporine in Severe Aplastic Anemia (SAA) Patients. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    The objective of this phase I/II study is to assess the safety of cyclophosphamide 120 mg/kg + low dose cyclosporine (100 - 200 micrograms per liter) as initial therapy in subjects with treatment-naïve SAA. We hypothesize that cyclophosphamide/ cyclosporine has activity in SAA with higher complete response rates with few instances of relapse and clonal evolution and could be a viable alternative treatment.

    The study will evaluate the safety and activity profile of cyclophosphamide/ cyclosporine in SAA. The safety endpoint will be toxicity profile after 6 months of treatment. The efficacy endpoint is complete response at 6 months.

Enrollment: 22
Study Start Date: August 2010
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAA hematologic response
Treatment-naive severe aplastic anemia patients will receive a low dose of cyclophosphamide (120mg/kg) and low dose cyclosporine ( target therapeutic level of 100-200 micrograms per liter). Cyclophosphamide will be given once daily for 4 doses. Cyclosporine will be started after cyclophosphamide completion, cyclosporine will be given twice daily. The dosing will be modified to attain the therapeutic level.
Drug: Cyclophosphamide
30 my/kg for 4 days
Other Name: Cytoxan
Drug: Cyclosporine
daily to a trough of 100 t0 200 ng/ml
Other Names:
  • Gengraf
  • Neoral
  • Sandimmune

  Show Detailed Description


Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Severe aplastic anemia characterized by:

Bone marrow cellularity less than 30 percent (excluding lymphocytes)


At least two of the following:

Absolute neutrophil count less than 500/ microL

Platelet count less than 20,000/ microL

Absolute reticulocyte count less than 60,000/ microL

Age greater than or equal to 2 years old

Weight greater than or equal to 12 kg


Diagnosis of Fanconi anemia

Cardiac ejection fraction less than 30 percent (evaluated by ECHO)

Evidence of a clonal hematologic bone marrow disorder on cytogenetics. Patients with the presence of trisomy 8, loss of Y or del(20q) will not be excluded in the absence of dysplastic changes in the marrow. Patients with very severe neutropenia (ANC less than 200 /microL) will not be excluded initially if cytogenetics are not available or pending. If evidence of a clonal disorder is later identified, the patient will go off study.

Prior immunosuppressive therapy with high dose Cy or ATG

Infection not adequately controlled with appropriate therapy

Serologic evidence of HIV infection

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 30 days is likely

Subjects with cancer who are not considered cured, are on active chemotherapeutic treatment or who take drugs with hematological effects

Current pregnancy or unwillingness to take oral contraceptives or refrain from pregnancy if of childbearing potential

Not able to understand the investigational nature of the study or to give informed consent.

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Please refer to this study by its identifier: NCT01193283

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: Danielle M Townsley, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Danielle Townsley, M.D., Hematology Clinician, National Institutes of Health Clinical Center (CC) Identifier: NCT01193283     History of Changes
Other Study ID Numbers: 100176, 10-H-0176
Study First Received: August 31, 2010
Results First Received: October 13, 2015
Last Updated: October 13, 2015
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Aplastic Anemia
Severe Aplastic Anemia

Additional relevant MeSH terms:
Anemia, Aplastic
Bone Marrow Diseases
Hematologic Diseases
Leukocyte Disorders
Alkylating Agents
Anti-Infective Agents
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on November 24, 2015