Sirolimus Treatment for Newly Diagnosed Primary Acquired PRCA
Study Details
Study Description
Brief Summary
Pure red cell aplasia (PRCA) is a kind of anemia characterized by severe reticulocytopenia and obvious bone marrow erythroblastic cells decreased. Cyclosporine A and /or steroids are the first line therapy but some patients were refractory or intolerance to the treatment. The effects of the second line therapy are also not satisfactory and sometimes not available. The investigators aim to explore the efficacy and side-effect of sirolimus for newly diagnosed primary acquired PRCA.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 4 |
Detailed Description
Pure red cell aplasia (PRCA) is a rare normocytic normochromic anemia with reticulocytopenia, characterized by a reduction of erythroid precursors from the bone marrow, could be divided into congenital and acquired PRCA according to pathogenesis. Congenital PRCA, also known as Diamond-Blackfan syndrome, has been associated with pathogenic variant in GATA1 and TSR2 and gene encode ribosomal proteins. Acquired PRCA can be a primary disease which is usually mediated by immunology, or secondary to other diseases, such as lymphoproliferative diseases, autoimmune diseases, thymoma, infection, or drugs. The first line therapy of acquired PRCA is Cyclosporine A (CsA) and steroids, the second line therapy are anti-CD20, anti-human thymocyte immunoglobulin, immunosuppressive drugs like cyclophosphamide, bone marrow transplantation. Unfortunately, some patients did not response or tolerate the above treatments.
Sirolimus (rapamycin) is an agent produced by the bacterium Streptomyces hygroscopicus, inhibits the mammalian target of rapamycin (mTOR). mTOR is a serine/threonine kinase that regulates cell growth, proliferation, metabolism and survival in eukaryotic cells, and is identified as two interacting complex, mTORC1 and mTORC2. Sirolimus primarily inhibits mTORC1, has been approved for prevent organ transplant rejection, especially in renal transplantation. Sirolimus also promises to treat autoimmune, degenerative and hyperproliferative disorders. Recently, sirolimus has been reported to be effective and well tolerated for many immune-mediated cytopenias, such as autoimmune lymphoproliferative syndrome, immune thrombocytopenia, EVANS syndrome, etc. Some case reports and our previous retrospective study showed that sirolimus was effective for refractory/relapse PRCA with good tolerance. However, due to the rare occurrence of PRCA and good response rate to CsA, there are very few studies of sirolimus on newly diagnosed PRCA so far.
In this study, It is anticipated to evaluate the effect and side effects of sirolimus on 20 patients with newly diagnosed PRCA compared with CsA. The side-effects will be documented and plasma concentration of sirolimus will be monitored.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Sirolimus on newly diagnosed primary acquired PRCA A prospective research of the sirolimus efficiency on newly diagnosed primary acquired PRCA patients. Sirolimus dosage: 2mg QD with plasma concentration 4-15ng/mL. Medication time should last at least 6 months |
Drug: Sirolimus
Sirolimus treats in experimental group
Other Names:
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Active Comparator: Cyclosporine A on newly diagnosed primary acquired PRCA Cyclosporine A (CsA) efficiency on newly diagnosed primary acquired PRCA patients. CsA dosage: 4mg/kg QD. Medication time should last at least 6 months |
Drug: Cyclosporine A
Cyclosporine A uses for active comparator group.
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Outcome Measures
Primary Outcome Measures
- Hemoglobin level [6 months]
Hemoglobin level in g/L
Secondary Outcome Measures
- Hemoglobin level [2 years]
Hemoglobin level in g/L
Eligibility Criteria
Criteria
Inclusion Criteria:
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Newly diagnosed primary acquired PRCA with no immunosuppression therapy.
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Excluding other diseases which might cause hematological abnormalities.
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With no abnormal heart function, active infection, and malignant tumors.
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Written informed consent.
Exclusion Criteria:
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NOT newly diagnosed primary acquired PRCA.
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Previous treatment of immunosuppression therapy.
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Patients who are under 18-year-old or over 70-year-old.
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Pregnant or lactating.
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Serious kidney and liver dysfunction (creatinine/transaminase ≥ 3 normal upper limit.
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Serious heart function failure.
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Merge on uncontrolled infection, other serious system diseases, and malignant tumors.
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Patients unwilling to or unable to comply with the protocol.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Peking Union Medical College Hospital | Beijing | China | 100730 |
Sponsors and Collaborators
- Bing Han
Investigators
- Principal Investigator: Bing Han, PhD, Peking Union Medical College Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRCA-2