Acalabrutinib Maleate and Bortezomib for Patients With HLA Antibodies (AB-HLA-2026)

Acalabrutinib Maleate Monotherapy or in Combination With Bortezomib for Eliminating HLA Antibodies in Patients With Hematologic Malignancies and Platelet Transfusion Refractoriness: a Multicenter, Randomized Controlled Study

Platelet transfusion refractoriness (PTR) is a common complication in patients with hematological malignancies. It not only prolongs the duration of platelet transfusion dependence and significantly increases the risk of bleeding, but is also strongly associated with graft failure and reduced survival after transplantation. HLA class I antibody-mediated alloimmunization is recognized as the most important immunological cause of PTR. HLA antibodies are directly secreted by plasma cells, which are derived from B cells. Therefore, targeting B cells to reduce antibody production is a crucial step in eliminating HLA antibodies. Bruton's tyrosine kinase (BTK) is expressed throughout B cell development from the pre-B cell stage to maturity and supports B cell development, maturation, survival, proliferation, and antibody production by acting as a downstream kinase in the B cell receptor signaling pathway. Bortezomib, a proteasome inhibitor, can selectively induce apoptosis in long-lived plasma cells. The investigators' preliminary exploratory use of a BTK inhibitor in the treatment of PTR with HLA antibodies significantly reduced the mean fluorescence intensity (MFI) of HLA antibodies, improved platelet transfusion outcomes, and demonstrated a favorable safety profile. Based on these findings, the investigators are conducting a prospective, multicenter, randomized controlled two-arm study to investigate the efficacy and safety of acalabrutinib and bortezomib in eliminating HLA antibodies in hematological malignancies patients with PTR.

Study Overview

• Status: Not yet recruiting
• Conditions: Hematological Malignancies; Platelet Transfusion Refractoriness (PTR); HLA Antibodies
• Intervention / Treatment: Drug: Acalabrutinib maleate; Drug: bortezomib; Other: HLA-matched or crossmatched irradiated platelets; Drug: human immune globulin

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yaqiong Tang; Phone Number: +8618896588075; Email: tangyaqiong@suda.edu.cn
• Study Contact Backup: Name: Xuefeng He; Phone Number: +8618914031640; Email: hexuefeng@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with hematological malignancies and platelet transfusion refractoriness (24-hour CCI < 4.5×10⁹/L or PPR < 20%), and with the highest MFI of HLA antibodies > 8000 ;
• Age 18-65 years, both male and female;
• ECOG performance status 0-3;
• Expected survival > 6 months;
• Patients must be able to understand and be willing to participate in this study, and sign an informed consent form.

Exclusion Criteria:

• Hypersensitivity to acalabrutinib, bortezomib, or excipients;
• Major organ bleeding (central nervous system, lung, intestines) or grade ≥3 bleeding;
• Hypersplenism;
• Concurrent use of drugs that may cause excessive platelet consumption (amphotericin B, vancomycin, ATG, interferon, etc.);
• Disseminated intravascular coagulation, microangiopathic hemolytic anemia;
• Underlying diseases of vital organs: such as malignant arrhythmia, myocardial infarction, chronic cardiac insufficiency, decompensated liver insufficiency, renal insufficiency, severe coagulation abnormalities, etc.; persistent fever (>38.0°C) for more than 3 days; clinically uncontrolled active infection (including bacterial, fungal, or viral infections), but patients under effective drug therapy are not excluded;
• Concurrent other progressive malignancies;
• Patients with cardiac insufficiency: ejection fraction (EF) <30%, NYHA class ≥III cardiac insufficiency;
• Pregnant or lactating women;
• Expected survival <60 days;
• Currently participating in other clinical drug trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Acalabrutinib maleate monotherapy or in combination with bortezomib	Drug: Acalabrutinib maleate; 100mg twice a day; Drug: bortezomib; 1.3mg/m2, d1,4,8,11; Other: HLA-matched or crossmatched irradiated platelets; Transfusion HLA-matched or crossmatched irradiated platelets 10U if platelet count lower than 10*109/L; Drug: human immune globulin; 0.4g/kg.d for 5 days
Active Comparator: Arm B; Transfusion of HLA-matched or crossmatched irradiated platelets	Other: HLA-matched or crossmatched irradiated platelets; Transfusion HLA-matched or crossmatched irradiated platelets 10U if platelet count lower than 10*109/L; Drug: human immune globulin; 0.4g/kg.d for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The response rate for anti-HLA antibody clearance	Complete response: HLA antibody MFI decrease ≥30% (applied to HLA antibody loci with baseline MFI >8000; median value used for assessment) Partial response: HLA antibody MFI decrease ≥10% and <30% No response: HLA antibody MFI decrease <10%, or no decrease or even an increase.	4 weeks after intervention
CCI (corrected count increments)	CCI = (platelet increment per ul) x (body surface area in m2)/number of platelets transfused (x 10E11)	4 weeks after intervention
PPR (percentage platelet recovery)	PPR = Post-transfusion platelet count-pre-transfusion platelet count (/L) × total blood volume × 100%	4 weeks after intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
The incidence of bleeding events	The study period (8 weeks after the initiation of intervention)
The overall survival rate	1 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Xuefeng He, the First Affiliated Hospital of Soochow University

Publications and helpful links

General Publications

• Pan Y, Zuo Y, Cui Q, Liu S, Dai H, Wu D, Jiang M, Tang X. Treatment outcome and efficacy of desensitization strategies for immunized-PTR in hematological malignancies before hematopoietic stem cell transplantation. Bone Marrow Transplant. 2026 Apr;61(4):437-444. doi: 10.1038/s41409-025-02749-1. Epub 2026 Jan 28.
• Van Osch TLJ, Oosterhoff JJ, Bentlage AEH, Nouta J, Koeleman CAM, Geerdes DM, Mok JY, Heidt S, Mulder A, Van Esch WJE, Kapur R, Porcelijn L, Van der Schoot CE, De Haas M, Wuhrer M, Voorberg J, Vidarsson G. Fc galactosylation of anti-platelet human IgG1 alloantibodies enhances complement activation on platelets. Haematologica. 2022 Oct 1;107(10):2432-2444. doi: 10.3324/haematol.2021.280493.
• Couvidou A, Rojas-Jimenez G, Dupuis A, Maitre B. Anti-HLA Class I alloantibodies in platelet transfusion refractoriness: From mechanisms and determinants to therapeutic prospects. Front Immunol. 2023 Feb 9;14:1125367. doi: 10.3389/fimmu.2023.1125367. eCollection 2023.
• Boothby AB, Tanner MK, Alswied A, Youngs D, Bribiesca Rodriguez J, Bikkani T, Cha N, Gernsheimer T, Gimferrer I, Hess JR, Sokol-Hessner L, Marivada S, Nash MG, Flegel WA, Vassallo RR, Stroncek DF, Tsang HC, Panch SR. Cumulative donor-specific antibody threshold predicts platelet transfusion response in HLA-alloimmunized patients. Blood Adv. 2024 Sep 10;8(17):4689-4699. doi: 10.1182/bloodadvances.2024014143.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 7, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: hematological malignancies; HLA antibodies; Platelet transfusion refractoriness
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Immunoglobulin Isotypes; Immunoglobulin G; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Bortezomib; Immunoglobulins, Intravenous
• Other Study ID Numbers: XFH2026-05

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
• product manufactured in and exported from the U.S.: No