Romiplostim in Combination With CsA vs. CsA in the Treatment of Newly Diagnosed NSAA

NCT06009497 | Unknown Phase 4

• 1 other identifier: Romiplostim-1
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic failure. Treatment options for patients with aplastic anemia are very limited. In a phase II/III, multicenter, open-label study exploring the efficacy and safety of romiplostim, the primary endpoint showed an overall response rate of 84% \[95% CI 66-95%\] at week 27. However, there are no prospective clinical data exploring whether romiplostim combined with ciclosporin (CsA) can further improve efficacy than ciclosporin monotherapy in newly diagnosed NSAA. Therefore, we aimed to compare the efficacy and safety of romiplostim in combination with CsA versus CsA monotherapy.

Conditions

Non Severe Aplastic Anemia

Outcome Measures

Primary Outcomes (2)

• overall response rate (ORR)

  Proportion of patients who achieved complete response and partial response.

  3, 6 months

• complete response rate (CRR)

  Proportion of patients who achieved complete response.

  3, 6 months

Secondary Outcomes (1)

• adverse event rate

  3, 6 months

Study Arms (2)

Romiplostim+CsA

EXPERIMENTAL

Romiplostim 10 µg/kg, subcutaneous injection, once a week, for at least 3 months. Patients with platelet count ≥50×109/L can stop using, and continue to use with platelet count \< 50×109/L. Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.

Drug: Romiplostim; Drug: Ciclosporin

CsA

EXPERIMENTAL

Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.

Drug: Ciclosporin

Interventions

Romiplostim DRUG

Romiplostim 10 µg/kg, subcutaneous injection, once a week.

Romiplostim+CsA

Ciclosporin DRUG

Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml.

CsA; Romiplostim+CsA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old.
• Clearly diagnosed as untreated NSAA.
• At least one of the following conditions was met at the time of enrollment: hemoglobin \<90 g/L. Platelet \<30×109/L, neutrophils \<1.0×109/L.
• Baseline liver and kidney function (ALT, AST, Cr) was less than 2 times the normal value.
• No active infection; Not pregnant or breastfeeding.
• Agree to sign the consent form.
• The Eastern Cancer Collaboration Group (ECOG) score was 0-2.

You may not qualify if:

• Pancytopenia caused by other causes, such as myelodysplastic syndrome (MDS).
• There is cytogenetic evidence of clonal hematologic bone marrow diseases (MDS, AML).
• PNH clone ≥50%.
• Had received hematopoietic stem cell transplantation (HSCT) before enrollment.
• Immunosuppressive therapy such as ATG or cyclosporine use for more than 2 weeks.
• Infection or bleeding that is not controlled by standard treatment.
• Allergic to recombinant TPO or Hitrepopar.
• Active HIV, HCV, HBV infection or cirrhosis, or portal hypertension.
• Any concomitant malignancy or local basal cell carcinoma of the skin within 5 years.
• Previous history of thromboembolic events, heart attack or stroke (including antiphospholipid antibody syndrome), and current use of anticoagulants.
• Women who are pregnant or nursing (lactation).
• Have participated in other clinical trials within 3 months

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking union medical college hospital

Beijing, China

Location

Related Publications (10)

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  PMID: 7616805 BACKGROUND

• Young NS. Aplastic Anemia. N Engl J Med. 2018 Oct 25;379(17):1643-1656. doi: 10.1056/NEJMra1413485. No abstract available.

  PMID: 30354958 BACKGROUND

• Bacigalupo A. How I treat acquired aplastic anemia. Blood. 2017 Mar 16;129(11):1428-1436. doi: 10.1182/blood-2016-08-693481. Epub 2017 Jan 17.

  PMID: 28096088 BACKGROUND

• Yang C, Zhang X. Incidence survey of aplastic anemia in China. Chin Med Sci J. 1991 Dec;6(4):203-7.

  PMID: 1813058 BACKGROUND

• Tichelli A, de Latour RP, Passweg J, Knol-Bout C, Socie G, Marsh J, Schrezenmeier H, Hochsmann B, Bacigalupo A, Samarasinghe S, Rovo A, Kulasekararaj A, Roth A, Eikema DJ, Bosman P, Bader P, Risitano A, Dufour C; SAA Working Party of the EBMT. Long-term outcome of a randomized controlled study in patients with newly diagnosed severe aplastic anemia treated with antithymocyte globulin and cyclosporine, with or without granulocyte colony-stimulating factor: a Severe Aplastic Anemia Working Party Trial from the European Group of Blood and Marrow Transplantation. Haematologica. 2020 May;105(5):1223-1231. doi: 10.3324/haematol.2019.222562. Epub 2019 Oct 3.

  PMID: 31582549 BACKGROUND

• Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013 Jul;98(1):10-23. doi: 10.1007/s12185-013-1382-0. Epub 2013 Jul 3.

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• Jing FM, Zhang XL, Meng FL, Liu XM, Shi Y, Qin P, Wang L, Zhou H, Hou Y, Song Q, Peng J, Hou M. Anti-c-Mpl antibodies in immune thrombocytopenia suppress thrombopoiesis and decrease response to rhTPO. Thromb Res. 2018 Oct;170:200-206. doi: 10.1016/j.thromres.2018.08.021. Epub 2018 Aug 30.

  PMID: 30199786 BACKGROUND

• Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopoietin receptor agonists: ten years later. Haematologica. 2019 Jun;104(6):1112-1123. doi: 10.3324/haematol.2018.212845. Epub 2019 May 9.

  PMID: 31073079 BACKGROUND

• Jang JH, Tomiyama Y, Miyazaki K, Nagafuji K, Usuki K, Uoshima N, Fujisaki T, Kosugi H, Matsumura I, Sasaki K, Kizaki M, Sawa M, Hidaka M, Kobayashi N, Ichikawa S, Yonemura Y, Enokitani K, Matsuda A, Ozawa K, Mitani K, Lee JW, Nakao S. Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II/III, multicentre, open-label study. Br J Haematol. 2021 Jan;192(1):190-199. doi: 10.1111/bjh.17190. Epub 2020 Nov 5.

  PMID: 33152120 BACKGROUND

• Ruan J, Zuo W, Chen M, Yang C, Han B. Eltrombopag is effective in patients with relapse/refractory aplastic anemia-report from a single center in China. Ann Hematol. 2020 Dec;99(12):2755-2761. doi: 10.1007/s00277-020-04266-1. Epub 2020 Sep 17.

  PMID: 32944791 BACKGROUND

MeSH Terms

Interventions

romiplostim; Cyclosporine

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Bing Han

CONTACT

13601059938; hanbing_li@sina.com.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: August 24, 2023
• Study Start: August 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: August 24, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)