Sirolimus Treatment for Refractory PRCA

• ClinicalTrials.gov Identifier: NCT03364764
• Recruitment Status: Completed
• First Posted: December 7, 2017
• Last Update Posted: July 6, 2021
• Sponsor: Bing Han
• Information provided by (Responsible Party): Bing Han, Peking Union Medical College Hospital

Tracking Information

• First Submitted Date: November 21, 2017
• First Posted Date: December 7, 2017
• Last Update Posted Date: July 6, 2021
• Actual Study Start Date: February 1, 2018
• Actual Primary Completion Date: February 1, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 1, 2017)

Hemoglobin level [ Time Frame: 6 months ]

Hemoglobin level in g/L

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 1, 2017)

Hemoglobin level [ Time Frame: 2 years ]

Hemoglobin level in g/L

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sirolimus Treatment for Refractory PRCA
• Official Title: Sirolimus Treatment for Refractory Pure Red Cell Aplasia, a Prospective Study
• Brief Summary: Pure red cell aplasia (PRCA) is a kind of anemia characterized by severe reticulocytopenia and obvious bone marrow erythroblastic cells decreased. Cyclosporine 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 refractory 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 and steroids, the second line therapy are anti-CD20, ATG, 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. However, due to the rare occurrence of PRCA and good response rate to cyclosporine, there are very few studies of sirolimus on refractory PRCA so far.

In this study, It is anticipate to evaluate the effect of sirolimus on 30 patients with refractory PRCA, the side-effects was documented and plasma concentration of sirolimus will be monitor.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pure Red Cell Aplasia

Intervention

Drug: Sirolimus

On refractory PRCA patients, sirolimus was tried. Dosage: 2mg QD for the first day, then 1 mg QD. Medication time should last at least 6 months.

Other Name: Sirolimus Tablets

Study Arms

Experimental: efficiency of sirolimus on PRCA

A prospective research of the sirolimus efficiency on refractory PRCA patients On refractory PRCA patients, sirolimus was tried. Dosage: 2mg QD for the first day, then 1 mg QD. Medication time should last at least 6 months.

Intervention: Drug: Sirolimus

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.
• Li 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.
• Means RT Jr. Pure red cell aplasia. Blood. 2016 Nov 24;128(21):2504-2509. doi: 10.1182/blood-2016-05-717140.
• Teachey 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 1, 2021): 64
• Original Estimated Enrollment (submitted: December 1, 2017): 30
• Actual Study Completion Date: May 1, 2021
• Actual Primary Completion Date: February 1, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Refractory pure red cell aplasia.
2. Excluding other diseases which might cause hematological abnormalities.
3. No response or intolerant to first and second line therapies.
4. 18-80 years old.
5. All subjects must: agree not to donate blood or be counseled about pregnancy precautions and risks of fetal exposure.
6. Written informed consent.

Exclusion Criteria:

1. NOT refractory pure red cell anemia.
2. Response and well tolerate to first or second line therapy.
3. Patients who are under 18-year-old or over 80-year-old.
4. Pregnant or lactating.
5. Patients unwilling to or unable to comply with the protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03364764
• Other Study ID Numbers: PRCA-1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bing Han, Peking Union Medical College Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Bing Han
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Peking Union Medical College Hospital
• Verification Date: June 2020