Tacrolimus Treatment for Refractory PRCA

Pure Red Cell Aplasia Clinical Trial

Official title:

Tacrolimus Treatment for Refractory Pure Red Cell Aplasia, a Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03540472
• Other study ID #: tacrolimus-001
• Status: Recruiting
• Phase: Phase 4
• Start date: June 10, 2018
• Est. completion date: June 10, 2020

Study information

• Verified date: May 2018
• Source: Peking Union Medical College Hospital
• Contact: Zhangbiao Long, M.D.
• Phone: +86 13011826728
• Email: longzhangbiao[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 tacrolimus for refractory PRCA.

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. Tacrolimus, also known as FK506, is an agent mainly used after allogeneic organ transplant to lower risk of organ rejection. Tacrolimus could inhibit the production the production of IL-2, and also used in the therapy of other T cell mediated diseases. Tacrolimus primarily has been approved for prevent organ transplant rejection, especially in renal transplantation, tacrolimus also promises to treat autoimmune, degenerative and hyperproliferative disorders. Recently, tacrolimus 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 tacrolimus on refractory PRCA so far. In this study, it is anticipate to evaluate the effect of tacrolimus on 30 patients with refractory PRCA, the side-effects was documented and plasma concentration of tacrolimus will be monitor.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 10, 2020
• Est. primary completion date: December 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Refractory pure red cell aplasia. 18-80 years old. No response or intolerant to first and second line therapies. Written informed consent.

Exclusion Criteria:

Other diseases which might cause hematological abnormalities. Response and well tolerate to first or second line therapy. Patients who are under 18-year-old or over 80-year-old. Pregnant or lactating. Patients unwilling to or unable to comply with the protocol.

Related Conditions & MeSH terms

• Pure Red Cell Aplasia
• Red-Cell Aplasia, Pure

Intervention

Drug:
• tacrolimus
On refractory PRCA patients, tacrolimus was tried. Dosage: 1mg bid and tacrolimus trough targets were 5-10 ng/ml throughout the study

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

Langer RM, Hené R, Vitko S, Christiaans M, Tedesco-Silva H Jr, Ciechanowski K, Cassuto E, Rostaing L, Vilatoba M, Machein U, Ulbricht B, Junge G, Dong G, Pascual J. Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multic — View Citation

Patsenker E, Schneider V, Ledermann M, Saegesser H, Dorn C, Hellerbrand C, Stickel F. Potent antifibrotic activity of mTOR inhibitors sirolimus and everolimus but not of cyclosporine A and tacrolimus in experimental liver fibrosis. J Hepatol. 2011 Aug;55( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemoglobin level	Hemoglobin level in g/L	6 months
Secondary	Hemoglobin level	Hemoglobin level in g/L	2 years