search
Back to results

Zanubrutinib in the Treatment of Relapsed/Refractory wAIHA

Primary Purpose

Warm Autoimmune Hemolytic Anemia

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Zanubrutinib
Sponsored by
Chen Miao
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Warm Autoimmune Hemolytic Anemia focused on measuring warm autoimmune hemolytic anemia, Zanubrutinib

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥18 years. Confirmed diagnosis of wAIHA or Evans syndrome, primary or secondary to connective tissue disease. If it is secondary, there are no other treatment indications for systemic involvement of primary connective tissue disease. No response or relapse after glucocorticoid treatment. Baseline liver and kidney function (ALT, AST, Cr) is less than 2 times the normal range. Consent to sign the informed consent form. Exclusion Criteria: Other important organ involvement in connective tissue disease. Uncontrolled infection or bleeding with standard treatment. Active HIV, HCV or HBV infection uncontrolled with standard treatment. Concurrent uncontrolled advanced malignant tumors or lymphoma. The subject is receiving any of the following drugs and has not met the following conditions of stable drug treatment duration at a fixed dose during screening: corticosteroids for at least 4 weeks; iron, vitamin B12 or folic acid for at least 4 weeks; Liver cirrhosis or portal hypertension. Pregnant or lactating women. Participation in other clinical trials within the last 3 months.

Sites / Locations

  • Peking Union Medical College Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zanubrutinib in the Treatment of Relapsed/Refractory wAIHA

Arm Description

Zanubrutinib 160mg, orally, twice daily, for a minimum of 3 months For effective patients, continue to use for 2 years after achieving optimal therapeutic effect.

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
ORR defined as the proportion of patients who met the criteria of either complete response (CR) or partial response (PR)
Complete response rate (CRR)
CRR defined as the proportion of patients who met the criteria of complete response.

Secondary Outcome Measures

Relapse rate
Relapse rate defined as the proportion of patients whose response shift from PR or CR to no response (NR).
Adverse events
Safety analyses include assessments of the incidence and severity of adverse events; all adverse events that occurred or worsened during the treatment period will be reported, as well as adverse events that occurred later but are considered by the investigator to be related to the trial drug.

Full Information

First Posted
June 20, 2023
Last Updated
June 20, 2023
Sponsor
Chen Miao
search

1. Study Identification

Unique Protocol Identification Number
NCT05922839
Brief Title
Zanubrutinib in the Treatment of Relapsed/Refractory wAIHA
Official Title
Zanubrutinib in Relapsed or Refractory Warm Autoimmune Hemolytic Anemia: a Prospective Cohort Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 2023 (Anticipated)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Chen Miao

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disorder characterized by the destruction of red blood cells through warm or cold antibodies. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. Bruton's tyrosine kinase (BTK) plays a crucial role in the signaling pathway of B-cell receptor (BCR), and has been found to be a major source of pathogenic signal transduction for various lymphoproliferative malignancies. The activity of BTK is related to the occurrence and progression of various B-cell lymphomas. Currently, BTK inhibitors are widely used in the treatment of B-cell lymphomas, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), and other B-cell lymphomas, showing significant efficacy. BTK affects the production of messenger molecules and regulates the BCR signaling pathway, causing B cells to transform into self-reactive B cells, which can trigger autoimmune diseases. Current research has shown that BTK activity increases in several autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) . Therefore, BTK inhibitors (BTKi) are important for the treatment of autoimmune diseases. Ibrutinib, one kind of BTKi, has been proven to treat secondary autoimmune hemolytic anemia (AIHA) in CLL and control CLL progression, and is an effective drug for treating lymphoma-associated AIHA . One kind of second-generation selective BTKi, acalabrutinib, can also reduce the incidence of AIHA in relapsed or refractory CLL patients. Currently, phase-II clinical studies exploring the treatment of AIHA using Ibrutinib, acalabrutinib, and rilzabrutinib, another BTKi, are underway. Zanubrutinib (BGB-3111, Brukinsa®, BeiGene) is a second-generation irreversible BTKi developed by Chinese company BeiGene. Compared to Ibrutinib, zanubrutinib has shown stronger effective activity and higher selectivity towards BTK, and weaker effects on other targets such as TEC, EGFR, and Src families, with low off-target side effects. Its efficacy, durability, oral absorption, and targeting are better than those of Ibrutinib. Zanubrutinib is approved for the treatment of various B-cell lymphomas, and clinical trials have shown excellent efficacy and tolerability in CLL and WM patients. In previously treated CLL patients, zanubrutinib exhibits better efficacy and safety than Ibrutinib. Currently, phase II clinical studies of zanubrutinib in ITP, antiphospholipid syndrome, IgG4-related immune diseases, and active proliferative lupus nephritis are underway. The therapeutic effect of zanubrutinib on refractory warm autoimmune hemolytic anemia, is worth exploring through exploratory research.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Warm Autoimmune Hemolytic Anemia
Keywords
warm autoimmune hemolytic anemia, Zanubrutinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Zanubrutinib in the Treatment of Relapsed/Refractory wAIHA
Arm Type
Experimental
Arm Description
Zanubrutinib 160mg, orally, twice daily, for a minimum of 3 months For effective patients, continue to use for 2 years after achieving optimal therapeutic effect.
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Intervention Description
Zanubrutinib 160mg, orally, twice daily, for a minimum of 3 months, and for effective patients, continue to use for 2 years after achieving optimal therapeutic effect.
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
ORR defined as the proportion of patients who met the criteria of either complete response (CR) or partial response (PR)
Time Frame
3/6 months
Title
Complete response rate (CRR)
Description
CRR defined as the proportion of patients who met the criteria of complete response.
Time Frame
3/6 months
Secondary Outcome Measure Information:
Title
Relapse rate
Description
Relapse rate defined as the proportion of patients whose response shift from PR or CR to no response (NR).
Time Frame
3/6 months
Title
Adverse events
Description
Safety analyses include assessments of the incidence and severity of adverse events; all adverse events that occurred or worsened during the treatment period will be reported, as well as adverse events that occurred later but are considered by the investigator to be related to the trial drug.
Time Frame
3/6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years. Confirmed diagnosis of wAIHA or Evans syndrome, primary or secondary to connective tissue disease. If it is secondary, there are no other treatment indications for systemic involvement of primary connective tissue disease. No response or relapse after glucocorticoid treatment. Baseline liver and kidney function (ALT, AST, Cr) is less than 2 times the normal range. Consent to sign the informed consent form. Exclusion Criteria: Other important organ involvement in connective tissue disease. Uncontrolled infection or bleeding with standard treatment. Active HIV, HCV or HBV infection uncontrolled with standard treatment. Concurrent uncontrolled advanced malignant tumors or lymphoma. The subject is receiving any of the following drugs and has not met the following conditions of stable drug treatment duration at a fixed dose during screening: corticosteroids for at least 4 weeks; iron, vitamin B12 or folic acid for at least 4 weeks; Liver cirrhosis or portal hypertension. Pregnant or lactating women. Participation in other clinical trials within the last 3 months.
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miao Chen
Phone
+86 13520112578
Email
chenm@pumch.cn
First Name & Middle Initial & Last Name & Degree
Bing Han
Phone
+86 69155028
Email
hanbingpumch@163.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31839434
Citation
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.
Results Reference
background
PubMed Identifier
23981017
Citation
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.
Results Reference
background
PubMed Identifier
33077936
Citation
Zarrin AA, Bao K, Lupardus P, Vucic D. Kinase inhibition in autoimmunity and inflammation. Nat Rev Drug Discov. 2021 Jan;20(1):39-63. doi: 10.1038/s41573-020-0082-8. Epub 2020 Oct 19.
Results Reference
background
PubMed Identifier
34803999
Citation
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.
Results Reference
background
PubMed Identifier
34534359
Citation
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.
Results Reference
background
PubMed Identifier
23058039
Citation
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.
Results Reference
background
PubMed Identifier
27252261
Citation
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.
Results Reference
background
PubMed Identifier
28157216
Citation
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.
Results Reference
background
PubMed Identifier
26442611
Citation
Rogers KA, Ruppert AS, Bingman A, Andritsos LA, Awan FT, Blum KA, Flynn JM, Jaglowski SM, Lozanski G, Maddocks KJ, Byrd JC, Woyach JA, Jones JA. Incidence and description of autoimmune cytopenias during treatment with ibrutinib for chronic lymphocytic leukemia. Leukemia. 2016 Feb;30(2):346-50. doi: 10.1038/leu.2015.273. Epub 2015 Oct 7.
Results Reference
background
PubMed Identifier
25716177
Citation
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.
Results Reference
background
PubMed Identifier
28203175
Citation
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.
Results Reference
background
PubMed Identifier
31876911
Citation
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.
Results Reference
background
PubMed Identifier
35628931
Citation
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.
Results Reference
background
PubMed Identifier
31381333
Citation
Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z. Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19.
Results Reference
background

Learn more about this trial

Zanubrutinib in the Treatment of Relapsed/Refractory wAIHA

We'll reach out to this number within 24 hrs