Acalabrutinib Maleate and Bortezomib for Patients With HLA Antibodies

NCT07635511 | Not Yet Recruiting Phase 3

• 1 other identifier: XFH2026-05
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hematological Malignancies; Platelet Transfusion Refractoriness (PTR); HLA Antibodies

Keywords

hematological malignancies; Platelet transfusion refractoriness; HLA antibodies

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• The incidence of bleeding events

  The study period (8 weeks after the initiation of intervention)

• The overall survival rate

  1 year

Study Arms (2)

Arm A

EXPERIMENTAL

Acalabrutinib maleate monotherapy or in combination with bortezomib

Drug: Acalabrutinib maleate; Drug: bortezomib; Other: HLA-matched or crossmatched irradiated platelets; Drug: human immune globulin

Arm B

ACTIVE COMPARATOR

Transfusion of HLA-matched or crossmatched irradiated platelets

Other: HLA-matched or crossmatched irradiated platelets; Drug: human immune globulin

Interventions

bortezomib DRUG

1.3mg/m2, d1,4,8,11

Arm A

human immune globulin DRUG

0.4g/kg.d for 5 days

Arm A; Arm B

Acalabrutinib maleate DRUG

100mg twice a day

Arm A

HLA-matched or crossmatched irradiated platelets OTHER

Transfusion HLA-matched or crossmatched irradiated platelets 10U if platelet count lower than 10\*109/L

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Related Publications (4)

• 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.

  PMID: 41606225 BACKGROUND

• 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.

  PMID: 35354253 BACKGROUND

• 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.

  PMID: 36845153 BACKGROUND

• 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.

  PMID: 39028936 BACKGROUND

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Bortezomib; Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Xuefeng He

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yaqiong Tang

CONTACT

+8618896588075; tangyaqiong@suda.edu.cn

Xuefeng He

CONTACT

+8618914031640; hexuefeng@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 9, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): May 31, 2029
• Last Updated: June 9, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share