Sirolimus Treatment for Newly Diagnosed Primary Acquired PRCA (PRCA)

February 26, 2023 updated by: Bing Han

Sirolimus Treatment for Newly Diagnosed Primary Acquired Pure Red Cell Aplasia: a Single Center Prospective Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100730
        • Peking Union Medical College Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 88 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. age >18 years old.
  2. hemoglobin (Hb) <90 g/L before treatment.
  3. no history of immunosuppression therapy prior to sirolimus or CsA treatment.
  4. adequate hepatic functions with alanine transaminase (ALT)/aspartate. transaminase (AST) levels within 3 times of the normal upper limit and total bilirubin levels within 2 times of the normal upper limit.
  5. documented patient consent.

Exclusion Criteria:

  1. diagnosis of secondary aPRCA.
  2. history of treatment with immunosuppression therapy before enrollment.
  3. history of leukemia, stem cell transplantation, or treatment-related myelodysplastic syndromes (MDS).
  4. creatinine/transaminase ≥ 3 normal upper limit.
  5. complicated with active or uncontrolled infections or uncontrolled cardiovascular disease.
  6. presence of other diseases that may cause anemia.
  7. presence of malignancies.
  8. pregnant and lactating women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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.
Other Names:
  • Cyclosporine A Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemoglobin level
Time Frame: 6 months
Hemoglobin level in g/L
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemoglobin level
Time Frame: 2 years
Hemoglobin level in g/L
2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response
Time Frame: 1 year
complete response plus partial response
1 year
Complete response
Time Frame: 1 year
Hemoglobin >120 g/L in males or Hemoglobin >110 g/L in females, and lasting for at least 2 months
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bing Han

Investigators

  • Principal Investigator: Bing Han, PhD, Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2020

Primary Completion (Actual)

July 30, 2022

Study Completion (Actual)

July 31, 2022

Study Registration Dates

First Submitted

July 9, 2020

First Submitted That Met QC Criteria

July 9, 2020

First Posted (Actual)

July 14, 2020

Study Record Updates

Last Update Posted (Estimate)

February 28, 2023

Last Update Submitted That Met QC Criteria

February 26, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRCA-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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