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Sirolimus Treatment for Newly Diagnosed Primary Acquired PRCA (PRCA)

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ClinicalTrials.gov Identifier: NCT04470804
Recruitment Status : Recruiting
First Posted : July 14, 2020
Last Update Posted : July 7, 2021
Sponsor:
Information provided by (Responsible Party):
Bing Han, Peking Union Medical College Hospital

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
Pure Red Cell Aplasia, Acquired Drug: Sirolimus Drug: Cyclosporine A 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sirolimus Treatment for Newly Diagnosed Primary Acquired Pure Red Cell Aplasia: a Single Center Prospective Study
Actual Study Start Date : August 1, 2020
Estimated Primary Completion Date : August 1, 2021
Estimated Study Completion Date : August 1, 2022


Arm Intervention/treatment
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 Name: Sirolimus Tablets

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.




Primary Outcome Measures :
  1. Hemoglobin level [ Time Frame: 6 months ]
    Hemoglobin level in g/L


Secondary Outcome Measures :
  1. Hemoglobin level [ Time Frame: 2 years ]
    Hemoglobin level in g/L



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Newly diagnosed primary acquired PRCA with no immunosuppression therapy.
  2. Excluding other diseases which might cause hematological abnormalities.
  3. With no abnormal heart function, active infection, and malignant tumors.
  4. Written informed consent.

Exclusion Criteria:

  1. NOT newly diagnosed primary acquired PRCA.
  2. Previous treatment of immunosuppression therapy.
  3. Patients who are under 18-year-old or over 70-year-old.
  4. Pregnant or lactating.
  5. Serious kidney and liver dysfunction (creatinine/transaminase ≥ 3 normal upper limit.
  6. Serious heart function failure.
  7. Merge on uncontrolled infection, other serious system diseases, and malignant tumors.
  8. Patients unwilling to or unable to comply with the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04470804


Contacts
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Contact: Yuzhou Huang, Bachlor +8618810915496 hyzxp1995@163.com
Contact: Yali Du, Master +8615845992396 yali_crazy@126.com

Locations
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China
Peking Union Medical College Hospital Recruiting
Beijing, China, 100730
Contact: Yali Du, Master    +8618910575941    yali_crazy@126.com   
Principal Investigator: Bing Han, Doctor         
Sponsors and Collaborators
Bing Han
Investigators
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Principal Investigator: Bing Han, PhD Peking Union Medical College Hospital
Publications of Results:
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Responsible Party: Bing Han, Professor, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT04470804    
Other Study ID Numbers: PRCA-2
First Posted: July 14, 2020    Key Record Dates
Last Update Posted: July 7, 2021
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bing Han, Peking Union Medical College Hospital:
sirolimus
newly diagnosed pure red cell aplasia
prospective study
Additional relevant MeSH terms:
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Red-Cell Aplasia, Pure
Anemia
Hematologic Diseases
Cyclosporine
Sirolimus
Cyclosporins
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Anti-Bacterial Agents
Antibiotics, Antineoplastic
Antineoplastic Agents