Hematological MalignanciesPhase 3AB-HLA-2026NCT07635511
Acalabrutinib Maleate and Bortezomib for Patients With HLA Antibodies
A Phase 3 study testing Acalabrutinib maleate, bortezomib and HLA-matched or crossmatched irradiated platelets in people with Hematological Malignancies and Platelet Transfusion Refractoriness (PTR), run by The First Affiliated Hospital of Soochow University.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hematological Malignancies, Platelet Transfusion Refractoriness (PTR), HLA Antibodies
- What is being tested?
- Acalabrutinib maleate, bortezomib and HLA-matched or crossmatched irradiated platelets
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2026to 31 May 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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.
- Being tested
- Acalabrutinib maleate, bortezomib, HLA-matched or crossmatched irradiated platelets, human immune globulin
- Keywords
- hematological malignancies, Platelet transfusion refractoriness, HLA antibodies
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acalabrutinib maleateDrug
100mg twice a day
bortezomibDrug
1.3mg/m2, d1,4,8,11
HLA-matched or crossmatched irradiated plateletsOther
Transfusion HLA-matched or crossmatched irradiated platelets 10U if platelet count lower than 10*109/L
human immune globulinDrug
0.4g/kg.d for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Acalabrutinib maleate monotherapy or in combination with bortezomib Receives: 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 Receives: Other: HLA-matched or crossmatched irradiated platelets; Drug: human immune globulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 4 weeks after intervention
PPR (percentage platelet recovery)
PPR = Post-transfusion platelet count-pre-transfusion platelet count (/L) × total blood volume × 100%
Measured: 4 weeks after intervention
Secondary outcomes (2)
The incidence of bleeding events
Measured: The study period (8 weeks after the initiation of intervention)
The overall survival rate
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2026
- Study start1 Jun 2026 (estimated)
- Primary completion1 Jan 2029 (estimated)
- Study completion31 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hematological MalignanciesStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital of Soochow UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xuefeng He, The First Affiliated Hospital of Soochow University
- Investigators
- Xuefeng He, Principal investigator, The First Affiliated Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07635511
- Sponsor's protocol ID
- XFH2026-05
- Acronym
- AB-HLA-2026
- Status last verified
- May 2026
- First submitted
- 1 Jun 2026
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 41606225Van 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.
PubMed 35354253Couvidou 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.
PubMed 36845153Boothby 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.
PubMed 39028936
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07635511
- Acronym / sponsor ID
- AB-HLA-2026 / XFH2026-05
- Keywords
- hematological malignancies, Platelet transfusion refractoriness, HLA antibodies
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Soochow UniversityUniversity, hospital or other
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 1 Jan 2029 (estimated)
- Study completion
- 31 May 2029 (estimated)
- First posted
- 9 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Acalabrutinib maleate, Drug: bortezomib, Other: HLA-matched or crossmatched irradiated platelets, Drug: human immune globulinAcalabrutinib maleate monotherapy or in combination with bortezomib |
| Arm B | Active comparator | Other: HLA-matched or crossmatched irradiated platelets, Drug: human immune globulinTransfusion of HLA-matched or crossmatched irradiated platelets |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acalabrutinib maleate100mg twice a day | Drug | Arm A |
| bortezomib1.3mg/m2, d1,4,8,11 | Drug | Arm A |
| HLA-matched or crossmatched irradiated plateletsTransfusion HLA-matched or crossmatched irradiated platelets 10U if platelet count lower than 10*109/L | Other | Arm A, Arm B |
| human immune globulin0.4g/kg.d for 5 days | Drug | Arm A, Arm B |
Primary outcome
The response rate for anti-HLA antibody clearance
Time frame: 4 weeks after intervention
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.
CCI (corrected count increments)
Time frame: 4 weeks after intervention
CCI = (platelet increment per ul) x (body surface area in m2)/number of platelets transfused (x 10E11)
PPR (percentage platelet recovery)
Time frame: 4 weeks after intervention
PPR = Post-transfusion platelet count-pre-transfusion platelet count (/L) × total blood volume × 100%
2 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Background: PubMed 41606225Pan 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.
- Background: PubMed 35354253Van 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.
- Background: PubMed 36845153Couvidou 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.
- Background: PubMed 39028936Boothby 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xuefeng He principal investigator
The First Affiliated Hospital of Soochow University
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Acalabrutinib maleate, bortezomib and HLA-matched or crossmatched irradiated platelets in people with Hematological Malignancies and Platelet Transfusion Refractoriness (PTR), run by The First Affiliated Hospital of Soochow University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yaqiong Tang (+8618896588075, tangyaqiong@suda.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The response rate for anti-HLA antibody clearance (time frame: 4 weeks after intervention). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07635511, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2026.