Orelabrutinib in the Treatment of Relapsed/Refractory AIHA

NCT07453368 | Recruiting Phase 2 DMC

• 1 other identifier: Orelabrutinib-AIHA
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.wAIHA Treatment Regimen: Group A (50mg group): Orelabrutinib 50 mg, orally, once daily. After 4 weeks of treatment, if still transfusion-dependent or hemoglobin increase is \< 20 g/L, the dose may be increased to 100 mg qd. Treatment can be discontinued if ineffective at 12 weeks.
2. 2.cAIHA Treatment Regimen: Group C (150mg group): Orelabrutinib 150 mg, orally, once daily. The treatment course is at least 12 weeks. Patients who respond and tolerate the drug well may continue treatment for up to 52 weeks or longer to observe long-term efficacy and safety.

Conditions

Autoimmune Hemolytic Anemia (AIHA)

Keywords

Autoimmune Hemolytic Anemia; Orelabrutinib; Treatment; Cohort Study

Outcome Measures

Primary Outcomes (1)

• ORR

  Overall Response Rate (ORR) at 12 weeks. Overall Response Rate (ORR) is defined as the proportion of patients achieving Complete Response (CR) + Partial Response (PR).

  12weeks

Secondary Outcomes (1)

• The incidence of adverse events

  12weeks

Study Arms (3)

wAIHA-A

EXPERIMENTAL

Orelabrutinib 50 mg, orally, once daily.After 4 weeks of treatment, if still transfusion-dependent or hemoglobin increase is \< 20 g/L, the dose may be increased to 100 mg qd. Treatment can be discontinued if ineffective at 12 weeks. Stable doses of glucocorticoids (e.g., prednisone ≤ 15 mg/day) are permitted, and their tapering process should be recorded.

Drug: Orelabrutinib-50

wAIHA-B

EXPERIMENTAL

Orelabrutinib 100 mg, orally, once daily. The treatment course is at least 12 weeks. Treatment can be discontinued if ineffective at 12 weeks. Patients who respond and tolerate the drug well may continue treatment for up to 52 weeks or longer to observe long-term efficacy and safety. Stable doses of glucocorticoids (e.g., prednisone ≤ 15 mg/day) are permitted, and their tapering process should be recorded.

Drug: Orelabrutinib-100

cAIHA-C

EXPERIMENTAL

Orelabrutinib 150 mg, orally, once daily. The treatment course is at least 12 weeks. Patients who respond and tolerate the drug well may continue treatment for up to 52 weeks or longer to observe long-term efficacy and safety.

Drug: Orelabrutinib-150

Interventions

Orelabrutinib-100 DRUG

Orelabrutinib 100 mg, orally, once daily. The treatment course is at least 12 weeks. Treatment can be discontinued if ineffective at 12 weeks. Patients who respond and tolerate the drug well may continue treatment for up to 52 weeks or longer to observe long-term efficacy and safety. Stable doses of glucocorticoids (e.g., prednisone ≤ 15 mg/day) are permitted, and their tapering process should be recorded.

Also known as: wAIHA-B

wAIHA-B

Orelabrutinib-150 DRUG

Orelabrutinib 150 mg, orally, once daily. The treatment course is at least 12 weeks. Patients who respond and tolerate the drug well may continue treatment for up to 52 weeks or longer to observe long-term efficacy and safety.

Also known as: wAIHA-C

cAIHA-C

Orelabrutinib-50 DRUG

Orelabrutinib 50 mg, orally, once daily. After 4 weeks of treatment, if still transfusion-dependent or hemoglobin increase is \< 20 g/L, the dose may be increased to 100 mg qd. Treatment can be discontinued if ineffective at 12 weeks. Stable doses of glucocorticoids (e.g., prednisone ≤ 15 mg/day) are permitted, and their tapering process should be recorded.

Also known as: wAIHA-A

wAIHA-A

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Patients with a definitive diagnosis of AIHA. wAIHA or Evans syndrome, primary or secondary to connective tissue disease (CTD) or lymphoproliferative disorder (LPD). If secondary, CTD should have no indication for treatment for other system involvement, and LPD should be in an asymptomatic, observation phase without treatment indication.
• cAIHA, primary or secondary to LPD. If secondary, LPD should be in an asymptomatic, observation phase without treatment indication.
• For wAIHA: No response (no partial response after 3 weeks) to full-dose glucocorticoid therapy (1-2 mg/kg/day), intolerance, or relapse (after initial response, hemoglobin drop ≥20 g/L or requiring re-initiation of immunosuppressive therapy). And hemoglobin ≤ 100 g/L.
• For cAIHA: No response or relapse after anti-CD20 monoclonal antibody therapy (after initial response, hemoglobin drop ≥20 g/L or recurrence of vascular symptoms, or requiring re-initiation of immunosuppressive therapy), or unsuitable for anti-CD20 therapy. And hemoglobin ≤ 100 g/L or presence of vascular symptoms.
• Baseline liver and kidney function (ALT, Cr) within 2 times the upper limit of normal (elevated AST, LDH, Bil due to hemolysis are not used as indicators for liver function assessment).
• Agreement to sign the informed consent form.

You may not qualify if:

• Active involvement of other major organs due to connective tissue disease.
• Uncontrolled infection or bleeding per standard treatment.
• Uncontrolled active HIV, HCV, or HBV infection per standard treatment.
• Concurrent advanced uncontrolled malignancy, lymphoma.
• Presence of other uncorrected types of anemia at screening, such as nutritional anemia, thalassemia, etc.
• Currently receiving glucocorticoid therapy at screening and unable to discontinue or taper to ≤ 15 mg/day (prednisone equivalent) within 1 week before enrollment.
• Currently receiving treatment with medications such as cyclosporine, tacrolimus, sirolimus, cyclophosphamide, azathioprine, stanozolol, testosterone undecanoate, danazol, etc., at screening, and the treatment duration at a stable dose is \< 12 weeks, or unable to discontinue directly.
• Last dose of rituximab \< 3 months prior to enrollment.
• Prior treatment with any BTK inhibitor.
• Liver cirrhosis or portal hypertension.
• Pregnant or breastfeeding women.
• Participation in another clinical trial within the past 3 months.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (15)

• Yan S, Zhou H, Huang R, Wang F, Mei H, Lin L, Guo J, Zhou X, Li Z, Liu Y, Li S, Zhou W, Hou Y, Hou M. A phase 2 trial of orelabrutinib showing promising efficacy and safety in patients with persistent or chronic primary immune thrombocytopenia. Am J Hematol. 2024 Jul;99(7):1392-1395. doi: 10.1002/ajh.27303. Epub 2024 Mar 28. No abstract available.

  PMID: 38546375 BACKGROUND

• Yu TS, Han SQ, Wang LJ, Wang HY, Ni XF, Wang RT, Li GS, Hou Y, Peng J, Yan ZY, Zhao YJ, Hou M, Liu XG. Effects of orelabrutinib, a BTK inhibitor, on antibody-mediated platelet destruction in primary immune thrombocytopenia. Br J Haematol. 2025 Apr;206(4):1186-1199. doi: 10.1111/bjh.20045. Epub 2025 Mar 11.

  PMID: 40069128 BACKGROUND

• Robak E, Robak T. Bruton's Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives. J Clin Med. 2022 May 16;11(10):2807. doi: 10.3390/jcm11102807.

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• Byrd JC, Wierda WG, Schuh A, Devereux S, Chaves JM, Brown JR, Hillmen P, Martin P, Awan FT, Stephens DM, Ghia P, Barrientos J, Pagel JM, Woyach JA, Burke K, Covey T, Gulrajani M, Hamdy A, Izumi R, Frigault MM, Patel P, Rothbaum W, Wang MH, O'Brien S, Furman RR. Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: updated phase 2 results. Blood. 2020 Apr 9;135(15):1204-1213. doi: 10.1182/blood.2018884940.

  PMID: 31876911 BACKGROUND

• Galinier A, Delwail V, Puyade M. Ibrutinib Is Effective in the Treatment of Autoimmune Haemolytic Anaemia in Mantle Cell Lymphoma. Case Rep Oncol. 2017 Jan 27;10(1):127-129. doi: 10.1159/000456002. eCollection 2017 Jan-Apr.

  PMID: 28203175 BACKGROUND

• Manda S, Dunbar N, Marx-Wood CR, Danilov AV. Ibrutinib is an effective treatment of autoimmune haemolytic anaemia in chronic lymphocytic leukaemia. Br J Haematol. 2015 Sep;170(5):734-6. doi: 10.1111/bjh.13328. Epub 2015 Feb 25. No abstract available.

  PMID: 25716177 BACKGROUND

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• Montillo M, O'Brien S, Tedeschi A, Byrd JC, Dearden C, Gill D, Brown JR, Barrientos JC, Mulligan SP, Furman RR, Cymbalista F, Plascencia C, Chang S, Hsu E, James DF, Hillmen P. Ibrutinib in previously treated chronic lymphocytic leukemia patients with autoimmune cytopenias in the RESONATE study. Blood Cancer J. 2017 Feb 3;7(2):e524. doi: 10.1038/bcj.2017.5. No abstract available.

  PMID: 28157216 BACKGROUND

• Iwata S, Tanaka Y. B-cell subsets, signaling and their roles in secretion of autoantibodies. Lupus. 2016 Jul;25(8):850-6. doi: 10.1177/0961203316643172.

  PMID: 27252261 BACKGROUND

• Liubchenko GA, Appleberry HC, Striebich CC, Franklin KE, Derber LA, Holers VM, Lyubchenko T. Rheumatoid arthritis is associated with signaling alterations in naturally occurring autoreactive B-lymphocytes. J Autoimmun. 2013 Feb;40:111-21. doi: 10.1016/j.jaut.2012.09.001. Epub 2012 Oct 8.

  PMID: 23058039 BACKGROUND

• McDonald C, Xanthopoulos C, Kostareli E. The role of Bruton's tyrosine kinase in the immune system and disease. Immunology. 2021 Dec;164(4):722-736. doi: 10.1111/imm.13416. Epub 2021 Oct 4.

  PMID: 34534359 BACKGROUND

• Ringheim GE, Wampole M, Oberoi K. Bruton's Tyrosine Kinase (BTK) Inhibitors and Autoimmune Diseases: Making Sense of BTK Inhibitor Specificity Profiles and Recent Clinical Trial Successes and Failures. Front Immunol. 2021 Nov 3;12:662223. doi: 10.3389/fimmu.2021.662223. eCollection 2021.

  PMID: 34803999 BACKGROUND

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  PMID: 33077936 BACKGROUND

• Birgens H, Frederiksen H, Hasselbalch HC, Rasmussen IH, Nielsen OJ, Kjeldsen L, Larsen H, Mourits-Andersen T, Plesner T, Ronnov-Jessen D, Vestergaard H, Klausen TW, Schollkopf C. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia. Br J Haematol. 2013 Nov;163(3):393-9. doi: 10.1111/bjh.12541. Epub 2013 Aug 24.

  PMID: 23981017 BACKGROUND

• Jager U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, Jilma B, Kuter DJ, Michel M, Montillo M, Roth A, Zeerleder SS, Berentsen S. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Rev. 2020 May;41:100648. doi: 10.1016/j.blre.2019.100648. Epub 2019 Dec 5.

  PMID: 31839434 BACKGROUND

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Miao Chen

  Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miao Chen

CONTACT

+86 18618230229; chenm@pumch.cn

Chuanhuan Liu

CONTACT

86+1323861016; LiuCH0310@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: March 1, 2026
• First Posted: March 6, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)