Tacrolimus Treatment for Refractory PRCA

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

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.

Study Overview

• Status: Unknown
• Conditions: Pure Red Cell Aplasia
• Intervention / Treatment: Drug: tacrolimus

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. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Zhangbiao Long, M.D.; Phone Number: +86 13011826728; Email: longzhangbiao@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: efficiency of tacrolimus on PRCA; A prospective research of the tacrolimus efficiency on refractory PRCA patients On refractory PRCA patients, tacrolimus was tried. Dosage: 1mg bid and tacrolimus trough targets were 5-10 ng/ml throughout the study. Medication time should last at least 6 months.	Drug: tacrolimus; On refractory PRCA patients, tacrolimus was tried. Dosage: 1mg bid and tacrolimus trough targets were 5-10 ng/ml throughout the study; Other Names: tacrolimus capsule

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Langer RM, Hene 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, multicentre trial in renal transplantation. Transpl Int. 2012 May;25(5):592-602. doi: 10.1111/j.1432-2277.2012.01465.x. Epub 2012 Mar 26.
• 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(2):388-98. doi: 10.1016/j.jhep.2010.10.044. Epub 2010 Dec 17.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 10, 2018
• Primary Completion (Anticipated): December 10, 2018
• Study Completion (Anticipated): June 10, 2020

Study Registration Dates

• First Submitted: May 14, 2018
• First Submitted That Met QC Criteria: May 28, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): May 30, 2018
• Last Update Submitted That Met QC Criteria: May 28, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: tacrolimus; prospective study; refractory pure red cell aplasia
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Red-Cell Aplasia, Pure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: tacrolimus-001

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