Sirolimus and Cyclosporine for Treatment-Resistant Aplastic Anemia
NCT ID: NCT00319878
Last Updated: 2008-10-07
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE1/PHASE2
52 participants
INTERVENTIONAL
2006-05-31
2009-12-31
Brief Summary
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Detailed Description
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This study will last at least 6 months. Participants will first be screened to verify diagnosis of aplastic anemia. The screening will include a physical examination, blood test, bone marrow biopsy from the pelvic bone, and review of medications and medical history. Individuals who are eligible will then start the first treatment period. Participants will receive two medications: cyclosporine will be taken twice a day and sirolimus will be taken once a day. Depending on side effects, the doses of either drug may be temporarily stopped or lowered. On Day 1, blood will be drawn and females will undergo a pregnancy test. Subsequent study visits will occur weekly for the first month, every 2 weeks for 2 months, and then once a month for the remainder of the study. Each visit will include a physical examination, vital sign assessment, and review of side effects and medications. Blood tests will be performed weekly for the first 3 weeks, and then every 2 weeks.
After 6 months of treatment, if a participant has shown improvements in disease status without major side effects, the treatment will continue. Over time the doses may be lowered. If a participant has not improved while on the study medication, treatment will stop at 6 months. Whenever treatment is discontinued, the participant will again undergo a physical examination, blood tests, and bone marrow biopsy.
Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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1
Participants will be treated with sirolimus and cyclosporine. In phase I, each dose cohort will initially enroll three patients. If no dose-limiting toxicity (DLT) is observed by Day 28 in any patient of a cohort, then 3 patients will be treated with the next highest sirolimus dose. If 1 out of 3 patients in any cohort experiences a DLT, then 3 more patients will be enrolled in that cohort. If no more patients have a DLT by Day 28, then sirolimus dose escalation will proceed. If one or more patients experience a DLT then that dose level will be considered to be the maximum tolerated sirolimus dose, and Phase II patients will be treated at the next lowest level. Cyclosporine will be given as a twice daily oral dose.
Sirolimus
Oral loading dose followed by a once daily dose:
* Cohort 1: Loading Dose - 1.2 mg; Daily Dose - 0.4 mg
* Cohort 2: % Dose Increase - 100%; Loading Dose - 2.4 mg; Daily Dose - 0.8 mg
* Cohort 3: % Dose Increase - 67%; Loading Dose - 3.9 mg; Daily Dose - 1.3 mg
* Cohort 4: % Dose Increase - 50%; Loading Dose - 6.0 mg; Daily Dose - 2.0 mg
Cyclosporine
Dose of 5 mg/kg divided as a twice daily oral dose
Interventions
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Sirolimus
Oral loading dose followed by a once daily dose:
* Cohort 1: Loading Dose - 1.2 mg; Daily Dose - 0.4 mg
* Cohort 2: % Dose Increase - 100%; Loading Dose - 2.4 mg; Daily Dose - 0.8 mg
* Cohort 3: % Dose Increase - 67%; Loading Dose - 3.9 mg; Daily Dose - 1.3 mg
* Cohort 4: % Dose Increase - 50%; Loading Dose - 6.0 mg; Daily Dose - 2.0 mg
Cyclosporine
Dose of 5 mg/kg divided as a twice daily oral dose
Eligibility Criteria
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Inclusion Criteria
* Falls within one of the following descriptions at the time of the original diagnosis:
1. For severe aplastic anemia, fulfills any two of the following three criteria: absolute neutrophil count less than 500/uL; absolute reticulocyte count less than 60,000/uL; and platelet count less than 20,000/uL
2. For moderate aplastic anemia, fulfills any two of the following three criteria: absolute neutrophil count less than 1200/ul; hemoglobin less than 8 g/dL with corrected reticulocyte count less than 1%; and platelet count less than 60,000/uL (Note: Participants who have progressed from moderate to severe aplastic anemia prior to study entry will be classified as having severe aplastic anemia)
* Diagnosis of refractory aplastic anemia, as defined by a failure to achieve at least a partial response to ATG within 6 months of treatment. Individuals who had a prior response to ATG but who have relapsed and not responded to salvage ATG are eligible. Individuals with relapsed disease who are not candidates for salvage ATG because they experienced a serious or life-threatening complication prior to ATG are also eligible.
* A Karnofsky performance status of at least 60%
* Adequate organ function, as defined by creatine levels less than 1.5 times the upper limit normal (ULN), and liver function tests (AST, bilirubin) less than 2 times the ULN
* Women of childbearing age must be willing to use effective contraception throughout the study
Exclusion Criteria
* Candidate for related allogeneic stem cell transplantation
* Active uncontrolled infection
* History of myelodysplastic syndrome or bone marrow cytogenetic abnormalities
* History of Fanconi's anemia or other congenital form of aplastic anemia
* Treatment with an investigational agent within 1 month of study entry
* HIV infection
* Pregnant or breastfeeding
21 Years
ALL
No
Sponsors
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Rare Diseases Clinical Research Network
NETWORK
Office of Rare Diseases (ORD)
NIH
Responsible Party
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UCLA Division of Hematology/Oncology
Locations
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UCLA Center for Health Sciences
Los Angeles, California, United States
Lee Moffitt Cancer Center
Tampa, Florida, United States
Taussig Cancer Center, Cleveland Clinic Foundation
Cleveland, Ohio, United States
Penn State University Cancer Center
Hershey, Pennsylvania, United States
Countries
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Central Contacts
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Lynn Tihopu
Role: CONTACT
Phone: 310-794-0738
Meenal Chalukya
Role: CONTACT
Phone: 310-825-8091
Facility Contacts
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Ronald Paquette, MD
Role: primary
Alan List, MD
Role: primary
Jaroslaw P. Maciejewski, MD
Role: primary
Thomas Loughran, MD
Role: primary
References
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Maciejewski JP, Risitano AM. Aplastic anemia: management of adult patients. Hematology Am Soc Hematol Educ Program. 2005:110-7. doi: 10.1182/asheducation-2005.1.110.
Young NS. Immunosuppressive treatment of acquired aplastic anemia and immune-mediated bone marrow failure syndromes. Int J Hematol. 2002 Feb;75(2):129-40. doi: 10.1007/BF02982017.
Brodsky RA, Chen AR, Brodsky I, Jones RJ. High-dose cyclophosphamide as salvage therapy for severe aplastic anemia. Exp Hematol. 2004 May;32(5):435-40. doi: 10.1016/j.exphem.2004.02.002.
Paquette RL. Diagnosis and management of aplastic anemia and myelodysplastic syndrome. Oncology (Williston Park). 2002 Sep;16(9 Suppl 10):153-61.
Other Identifiers
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BMF 5403
Identifier Type: -
Identifier Source: secondary_id
RDCRN 5403
Identifier Type: -
Identifier Source: org_study_id