Phase 2 N=22 Treatment

Cyclophosphamide Plus Cyclosporine in Treatment-Naive Severe Aplastic Anemia

Aplastic Anemia · Neutropenia · Pancytopenia · Severe Aplastic Anemia

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View on ClinicalTrials.gov: NCT01193283 ↗

Enrolled (actual)

Serious AEs

72.7%

Results posted

Nov 2015

Primary outcome: Primary: Blood Counts and Adverse Event Profile After 6 Months of Treatment. — 4; 5; 12 participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Cyclophosphamide (Drug); Cyclosporine (Drug)
Age: Pediatric, Adult, Older Adult · 2+ yrs
Sex: All
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Primary completion: Sep 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY Blood Counts and Adverse Event Profile After 6 Months of Treatment.	4; 5; 12	—

Summary

Background: * 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. Objectives: - 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.

Eligibility Criteria

INCLUSION CRITERIA:

Severe aplastic anemia characterized by:

Bone marrow cellularity less than 30 percent (excluding lymphocytes)

AND

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

EXCLUSION CRITERIA

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01193283). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.