Cyclophosphamide Plus Cyclosporine in Treatment-Naive Severe Aplastic Anemia
2 other identifiers
interventional
22
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Aug 2010
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2010
CompletedFirst Submitted
Initial submission to the registry
August 31, 2010
CompletedFirst Posted
Study publicly available on registry
September 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2014
CompletedResults Posted
Study results publicly available
November 11, 2015
CompletedMay 22, 2017
April 1, 2017
4.1 years
August 31, 2010
October 13, 2015
April 11, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Blood Counts and Adverse Event Profile After 6 Months of Treatment.
The safety endpoint will be toxicity profile after 6 months of treatment. The efficacy endpoint is complete response rate at 6 months, with complete response defined as blood counts no longer meeting the standard criteria for severe pancytopenia in severe aplastic anemia.
6 months
Study Arms (1)
SAA hematologic response
EXPERIMENTALTreatment-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.
Interventions
daily to a trough of 100 t0 200 ng/ml
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (5)
Rosenfeld S, Follmann D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA. 2003 Mar 5;289(9):1130-5. doi: 10.1001/jama.289.9.1130.
PMID: 12622583BACKGROUNDYoung NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006 Oct 15;108(8):2509-19. doi: 10.1182/blood-2006-03-010777. Epub 2006 Jun 15.
PMID: 16778145BACKGROUNDScheinberg P, Nunez O, Wu C, Young NS. Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil. Br J Haematol. 2006 Jun;133(6):606-11. doi: 10.1111/j.1365-2141.2006.06085.x.
PMID: 16704434BACKGROUNDZaimoku Y, Patel BA, Adams SD, Shalhoub R, Groarke EM, Lee AAC, Kajigaya S, Feng X, Rios OJ, Eager H, Alemu L, Quinones Raffo D, Wu CO, Flegel WA, Young NS. HLA associations, somatic loss of HLA expression, and clinical outcomes in immune aplastic anemia. Blood. 2021 Dec 30;138(26):2799-2809. doi: 10.1182/blood.2021012895.
PMID: 34724566DERIVEDScheinberg P, Townsley D, Dumitriu B, Scheinberg P, Weinstein B, Daphtary M, Rios O, Wu CO, Young NS. Moderate-dose cyclophosphamide for severe aplastic anemia has significant toxicity and does not prevent relapse and clonal evolution. Blood. 2014 Oct 30;124(18):2820-3. doi: 10.1182/blood-2014-05-573642. Epub 2014 Sep 3.
PMID: 25185712DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Danielle Townsley
- Organization
- NIH NHLBI
Study Officials
- PRINCIPAL INVESTIGATOR
Danielle M Townsley, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Hematology Clinician
Study Record Dates
First Submitted
August 31, 2010
First Posted
September 1, 2010
Study Start
August 1, 2010
Primary Completion
September 1, 2014
Study Completion
September 1, 2014
Last Updated
May 22, 2017
Results First Posted
November 11, 2015
Record last verified: 2017-04