Sirolimus Treatment for Newly Diagnosed Primary Acquired PRCA
Condition: Pure Red Cell Aplasia, Acquired
MeSH terms: Red-Cell Aplasia, Pure
Study type: Interventional
Phase: Phase 4

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.
    

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 efficacy and safety of sirolimus versus CsA
      in patients with newly diagnosed PRCA . The side-effects will be documented and plasma
      concentration of sirolimus will be monitored. Furthermore, an interim analysis will be
      performed to assess the treatment efficacy and safety of sirolimus versus CsA in primary PRCA
      patients when a total of 56 eligible participants finished the designed treatment.
    

Intervention name(s): Sirolimus; Cyclosporine A
Intervention type(s): Drug; Drug
Intervention description(s): Sirolimus treats in experimental group; Cyclosporine A uses for active comparator group.
Other intervention name(s): Sirolimus Tablets; Cyclosporine A Tablets
Intervention MeSH terms: Cyclosporine; Sirolimus; Temsirolimus; MTOR Inhibitors; Cyclosporins
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: sirolimus; newly diagnosed pure red cell aplasia; prospective study