Acalabrutinib Maleate and Bortezomib for Patients With HLA Antibodies
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Acalabrutinib maleate, bortezomib, HLA-matched or crossmatched irradiated platelets, human immune globulin.
- Who it may be relevant to
- Registry conditions: Hematological Malignancies, Platelet Transfusion Refractoriness (PTR), HLA Antibodies. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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
Overview
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.
Interventions
- 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
Primary outcome measures
- The response rate for anti-HLA antibody clearance [Time frame: 4 weeks after intervention]
- CCI (corrected count increments) [Time frame: 4 weeks after intervention]
- PPR (percentage platelet recovery) [Time frame: 4 weeks after intervention]
Secondary outcome measures (2)
- The incidence of bleeding events [Time frame: The study period (8 weeks after the initiation of intervention)]
- The overall survival rate [Time frame: 1 year]
Eligibility criteria
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
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. PMID 41606225
- 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
- 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
- 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.2 PMID 39028936
Identifiers
NCT: NCT07635511 · XFH2026-05