Pure Red Cell Aplasia, AcquiredPhase 4PRCANCT04470804
Sirolimus Treatment for Newly Diagnosed Primary Acquired PRCA
A Phase 4 study testing Sirolimus and Cyclosporine A in people with Pure Red Cell Aplasia, Acquired, run by Bing Han at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 88 years
- Conditions the study is for
- Pure Red Cell Aplasia, Acquired
- What is being tested?
- Sirolimus and Cyclosporine A
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2020to 31 Jul 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 88 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age >18 years old.
- hemoglobin (Hb) <90 g/L before treatment.
- no history of immunosuppression therapy prior to sirolimus or CsA treatment.
- 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.
- documented patient consent.
Who cannot join
- diagnosis of secondary aPRCA.
- history of treatment with immunosuppression therapy before enrollment.
- history of leukemia, stem cell transplantation, or treatment-related myelodysplastic syndromes (MDS).
- creatinine/transaminase ≥ 3 normal upper limit.
- complicated with active or uncontrolled infections or uncontrolled cardiovascular disease.
- presence of other diseases that may cause anemia.
- presence of malignancies.
- pregnant and lactating women.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Pure Red Cell Aplasia, Acquired
- Being tested
- Sirolimus, Cyclosporine A
- Keywords
- sirolimus, newly diagnosed pure red cell aplasia, prospective study
- Medical subject headings
- Red-Cell Aplasia, Pure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Sirolimus Tablets
Sirolimus treats in experimental group
Cyclosporine ADrug
Also called Cyclosporine A Tablets
Cyclosporine A uses for active comparator group.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus on newly diagnosed primary acquired PRCA | Experimental | 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 Receives: Drug: Sirolimus |
| Cyclosporine A on newly diagnosed primary acquired PRCA | Active comparator | Cyclosporine A (CsA) efficiency on newly diagnosed primary acquired PRCA patients. CsA dosage: 4mg/kg QD. Medication time should last at least 6 months Receives: Drug: Cyclosporine A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemoglobin level
Hemoglobin level in g/L
Measured: 6 months
Secondary outcomes (1)
Hemoglobin level
Hemoglobin level in g/L
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2020
- Study start1 Jul 2020
- Primary completion30 Jul 2022
- Study completion31 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Pure Red Cell Aplasia, AcquiredStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bing Han
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Bing Han, Peking Union Medical College Hospital
- Investigators
- Bing Han, PhD, Principal investigator, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04470804
- Sponsor's protocol ID
- PRCA-2
- Acronym
- PRCA
- Status last verified
- Feb 2023
- First submitted
- 9 Jul 2020
- Last updated
- 28 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bride KL, Vincent T, Smith-Whitley K, Lambert MP, Bleesing JJ, Seif AE, Manno CS, Casper J, Grupp SA, Teachey DT. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 2016 Jan 7;127(1):17-28. doi: 10.1182/blood-2015-07-657981. Epub 2015 Oct 26.
PubMed 26504182Li J, Wang Z, Dai L, Cao L, Su J, Zhu M, Yu Z, Bai X, Ruan C. Effects of rapamycin combined with low dose prednisone in patients with chronic immune thrombocytopenia. Clin Dev Immunol. 2013;2013:548085. doi: 10.1155/2013/548085. Epub 2013 Dec 2.
PubMed 24363761Means RT Jr. Pure red cell aplasia. Blood. 2016 Nov 24;128(21):2504-2509. doi: 10.1182/blood-2016-05-717140.
PubMed 27881371Teachey DT, Greiner R, Seif A, Attiyeh E, Bleesing J, Choi J, Manno C, Rappaport E, Schwabe D, Sheen C, Sullivan KE, Zhuang H, Wechsler DS, Grupp SA. Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br J Haematol. 2009 Apr;145(1):101-6. doi: 10.1111/j.1365-2141.2009.07595.x. Epub 2009 Feb 4.
PubMed 19208097Long Z, Yu F, Du Y, Li H, Chen M, Zhuang J, Han B. Successful treatment of refractory/relapsed acquired pure red cell aplasia with sirolimus. Ann Hematol. 2018 Nov;97(11):2047-2054. doi: 10.1007/s00277-018-3431-5. Epub 2018 Jul 7.
PubMed 29982851Chen Z, Liu X, Chen M, Yang C, Han B. Successful sirolimus treatment of patients with pure red cell aplasia complicated with renal insufficiency. Ann Hematol. 2020 Apr;99(4):737-741. doi: 10.1007/s00277-020-03946-2. Epub 2020 Feb 6.
PubMed 32030447Yang Y, Tang Z, Huang Y, Hu Q, Wang S, Ji J, Du Y, Yang C, Chen M, Hu S, Han B. Sirolimus versus cyclosporine A in patients with primary acquired pure red cell aplasia: a prospective cohort study. Blood Cancer J. 2023 May 10;13(1):74. doi: 10.1038/s41408-023-00845-3. No abstract available.
PubMed 37160872
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sirolimus Treatment for Newly Diagnosed Primary Acquired Pure Red Cell Aplasia: a Single Center Prospective Study
- ClinicalTrials.gov ID
- NCT04470804
- Acronym / sponsor ID
- PRCA / PRCA-2
- Conditions
- Pure Red Cell Aplasia, Acquired
- Keywords
- sirolimus, newly diagnosed pure red cell aplasia, prospective study
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Bing HanUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 30 Jul 2022 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 14 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus on newly diagnosed primary acquired PRCA | Experimental | Drug: SirolimusA 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 |
| Cyclosporine A on newly diagnosed primary acquired PRCA | Active comparator | Drug: Cyclosporine ACyclosporine A (CsA) efficiency on newly diagnosed primary acquired PRCA patients. CsA dosage: 4mg/kg QD. Medication time should last at least 6 months |
Who may qualify
- Ages
- 18 to 88 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- age >18 years old.
- hemoglobin (Hb) <90 g/L before treatment.
- no history of immunosuppression therapy prior to sirolimus or CsA treatment.
- 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.
- documented patient consent.
Key exclusion criteria (8 listed)
- diagnosis of secondary aPRCA.
- history of treatment with immunosuppression therapy before enrollment.
- history of leukemia, stem cell transplantation, or treatment-related myelodysplastic syndromes (MDS).
- creatinine/transaminase ≥ 3 normal upper limit.
- complicated with active or uncontrolled infections or uncontrolled cardiovascular disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: Sirolimus TabletsSirolimus treats in experimental group | Drug | Sirolimus on newly diagnosed primary acquired PRCA |
| Cyclosporine AAlso: Cyclosporine A TabletsCyclosporine A uses for active comparator group. | Drug | Cyclosporine A on newly diagnosed primary acquired PRCA |
Primary outcome
Hemoglobin level
Time frame: 6 months
Hemoglobin level in g/L
1 secondary outcome
Hemoglobin level
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.
- Results publication: PubMed 26504182Bride KL, Vincent T, Smith-Whitley K, Lambert MP, Bleesing JJ, Seif AE, Manno CS, Casper J, Grupp SA, Teachey DT. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 2016 Jan 7;127(1):17-28. doi: 10.1182/blood-2015-07-657981. Epub 2015 Oct 26.
- Results publication: PubMed 24363761Li J, Wang Z, Dai L, Cao L, Su J, Zhu M, Yu Z, Bai X, Ruan C. Effects of rapamycin combined with low dose prednisone in patients with chronic immune thrombocytopenia. Clin Dev Immunol. 2013;2013:548085. doi: 10.1155/2013/548085. Epub 2013 Dec 2.
- Results publication: PubMed 27881371Means RT Jr. Pure red cell aplasia. Blood. 2016 Nov 24;128(21):2504-2509. doi: 10.1182/blood-2016-05-717140.
- Results publication: PubMed 19208097Teachey DT, Greiner R, Seif A, Attiyeh E, Bleesing J, Choi J, Manno C, Rappaport E, Schwabe D, Sheen C, Sullivan KE, Zhuang H, Wechsler DS, Grupp SA. Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br J Haematol. 2009 Apr;145(1):101-6. doi: 10.1111/j.1365-2141.2009.07595.x. Epub 2009 Feb 4.
- Results publication: PubMed 29982851Long Z, Yu F, Du Y, Li H, Chen M, Zhuang J, Han B. Successful treatment of refractory/relapsed acquired pure red cell aplasia with sirolimus. Ann Hematol. 2018 Nov;97(11):2047-2054. doi: 10.1007/s00277-018-3431-5. Epub 2018 Jul 7.
- Results publication: PubMed 32030447Chen Z, Liu X, Chen M, Yang C, Han B. Successful sirolimus treatment of patients with pure red cell aplasia complicated with renal insufficiency. Ann Hematol. 2020 Apr;99(4):737-741. doi: 10.1007/s00277-020-03946-2. Epub 2020 Feb 6.
- Derived from this study: PubMed 37160872Yang Y, Tang Z, Huang Y, Hu Q, Wang S, Ji J, Du Y, Yang C, Chen M, Hu S, Han B. Sirolimus versus cyclosporine A in patients with primary acquired pure red cell aplasia: a prospective cohort study. Blood Cancer J. 2023 May 10;13(1):74. doi: 10.1038/s41408-023-00845-3. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bing Han, PhD principal investigator
Peking Union Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sirolimus and Cyclosporine A in people with Pure Red Cell Aplasia, Acquired, run by Bing Han at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hemoglobin level (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04470804, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2023.