Hemophagocytic LymphohistiocytosisPhase 4NCT07270835
Zanubrutinib Combined With Rituximab in the Treatment of Secondary HLH in B-cell Lymphoma
A Phase 4 study testing Rituximab and Zanubrutinib in people with Hemophagocytic Lymphohistiocytosis and B Cell Lymphoma, run by The First Affiliated Hospital of Soochow University at 1 site in China.
Trial summary
For patients who met the inclusion criteria, treatment regimens were administered: Rituximab 375 mg/m², intravenously, once weekly for 4 weeks. Zanubrutinib 160 mg, orally, twice daily for 4 weeks. Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate. Read more about this study
- Who is it for?
- Ages 14 to 80 years
- Conditions the study is for
- Hemophagocytic Lymphohistiocytosis, B Cell Lymphoma
- What is being tested?
- Rituximab and Zanubrutinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2025to Aug 2027
- Phase
- Phase 4
- 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 14 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- According to the diagnostic criteria of HLH-04, the patients meet the diagnostic criteria of HLH;
- HLH patients with definite or highly suspected evidence of B-cell lymphoma; Or HLH patients whose bone marrow flow cytometry show an increased proportion of CD20-positive B cells;
- Age of 14-80 years old, both sexes;
- Predicted survival beyond 1 month;
- Baseline serum creatinine ≤1.5 times ULN; Fibrinogen could be corrected to ≥0.6g/L by infusion;
- Negative serum HIV antibody; Either negative for HCV antibodies or positive for HCV antibodies but negative for HCV RNA. HBV surface antigen and HBV core antibody were negative. If any of the above was positive, HBV DNA titer in peripheral blood should be tested, and the titer was less than 1×10^3 copies /ml;
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- Left ventricular ejection fraction (LVEF) ≥50% measured by echocardiography;
- The patient have no serious and uncontrollable infections, such as pulmonary infection, intestinal infection, and sepsis;
- Women of childbearing age must be confirmed to be not pregnant by pregnancy test and willing to take effective measures to prevent pregnancy during the study period and ≥12 months after the last dose; Pregnant and lactating women cannot participate; All male subjects took contraceptive measures during the trial and ≥3 months after the last dose;
- Patients should be able to sign informed consent.
Who cannot join
- Patients with known severe allergy to rituximab, zanubrutinib, or other BTK inhibitors;
- Severe active infections (including bacterial, viral or fungal infections) or uncontrolled co-infections;
- Severe organ dysfunction including NYHA class III-IV heart failure or severe arrhythmia; Liver function: ALT or AST >5 times the upper limit, or severe cirrhosis; Renal function: CrCl <30 mL/min or severe renal insufficiency;
- Combined with other malignant tumors and the expected survival time was less than 3 months;
- Have received other experimental drugs and had not completed the drug washout period;
- Pregnant or lactating women, or unwilling to use effective contraception;
- any condition that would not be suitable for participation in the study or that might affect adherence, follow-up, or safety assessment, as judged by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu
Xuefeng He, doctor, hexuefeng@suda.edu.cn
Fei Zhou, doctor, zhoufei@suda.edu.cn
About this study
Official title: The Study of Zanubrutinib Combined With Rituximab in the Treatment of Secondary Hemophagocytic Lymphohistiocytosis in B-cell Lymphoma
For patients who met the inclusion criteria, treatment regimens were administered: Rituximab 375 mg/m², intravenously, once weekly for 4 weeks.
Zanubrutinib 160 mg, orally, twice daily for 4 weeks. Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate.
Read the detailed description
For patients who met the inclusion criteria, treatment regimens were administered:
Rituximab 375 mg/m², intravenously, once weekly for 4 weeks (may be extended or adjusted according to clinical response).
Zanubrutinib: 160 mg, orally, twice daily for 4 weeks as for rutuximab. Dose can be adjusted or extended according to tolerance and efficacy.
When ≥3 grade hematological or intolerable non-hematological toxicity occur, zanubrutinib or rituximab will be suspended, and the dose will be reduced or resumed according to the toxicity grade after recovery. The dose of zanubrutinib should be adjusted according to the manufacturer's label with concomitant use of strong CYP3A inhibitor/inducer.
Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate.
- Being tested
- Rituximab, Zanubrutinib
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called HALPRYZA
375 mg/m², intravenously, once weekly for 4 weeks
ZanubrutinibDrug
Also called Brukinsa
160 mg, orally, twice daily for 4 weeks as for rutuximab.
| Study group | Role | What they receive |
|---|---|---|
| intervention group | Experimental | Rituximab 375 mg/m², intravenously, once weekly for 4 weeks (may be extended or adjusted according to clinical response).
Zanubrutinib: 160 mg, orally, twice daily for 4 weeks as for rutuximab. Dose can be adjusted or extended according to tolerance and efficacy.
When ≥3 grade hematological or intolerable non-hematological toxicity occur, zanubrutinib or rituximab will be suspended, and the dose will be reduced or resumed according to the toxicity grade after recovery. The dose of zanubrutinib should be adjusted according to the manufacturer's label with concomitant use of strong CYP3A inhibitor/inducer.
Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate. Receives: Drug: Rituximab; Drug: Zanubrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
response rate of HLH after 4 weeks of treatment
RR will be evaluated according to the response evaluation criteria recommended by the International Histiocyte Society.
Measured: after 4 weeks
OS at week 8
overall survival after 8 weeks of treatment
Measured: after 8 weeks
Secondary outcomes (2)
AE
Adverse events will be evaluated according to NCI-CTCAE 5.0.
Measured: till the end of 4 weeks
OS
OS at 1/2/3 months/ 6 months
Measured: at 4/8/12/24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2025
- Study start1 Nov 2025
- Primary completionApr 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophagocytic LymphohistiocytosisStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 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, doctor, Principal investigator, department of hematology, The First Affiliated Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07270835
- Sponsor's protocol ID
- HLH-003
- Status last verified
- Nov 2025
- First submitted
- 18 Nov 2025
- Last updated
- 8 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Study of Zanubrutinib Combined With Rituximab in the Treatment of Secondary Hemophagocytic Lymphohistiocytosis in B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT07270835
- Acronym / sponsor ID
- HLH-003
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Soochow UniversityUniversity, hospital or other
- Study start
- 1 Nov 2025 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 8 Dec 2025 (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.
For patients who met the inclusion criteria, treatment regimens were administered: Rituximab 375 mg/m², intravenously, once weekly for 4 weeks.
Zanubrutinib 160 mg, orally, twice daily for 4 weeks. Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate.
Detailed description
For patients who met the inclusion criteria, treatment regimens were administered:
Rituximab 375 mg/m², intravenously, once weekly for 4 weeks (may be extended or adjusted according to clinical response).
Zanubrutinib: 160 mg, orally, twice daily for 4 weeks as for rutuximab. Dose can be adjusted or extended according to tolerance and efficacy.
When ≥3 grade hematological or intolerable non-hematological toxicity occur, zanubrutinib or rituximab will be suspended, and the dose will be reduced or resumed according to the toxicity grade after recovery. The dose of zanubrutinib should be adjusted according to the manufacturer's label with concomitant use of strong CYP3A inhibitor/inducer.
Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intervention group | Experimental | Drug: Rituximab, Drug: ZanubrutinibRituximab 375 mg/m², intravenously, once weekly for 4 weeks (may be extended or adjusted according to clinical response). Zanubrutinib: 160 mg, orally, twice daily for 4 weeks as for rutuximab. Dose can be adjusted or extended according to tolerance and efficacy. When ≥3 grade hematological or intolerable non-hematological toxicity occur, zanubrutinib or rituximab will be suspended, and the dose will be reduced or resumed according to the toxicity grade after recovery. The dose of zanubrutinib should be adjusted according to the manufacturer's label with concomitant use of strong CYP3A inhibitor/inducer. Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate. |
Who may qualify
- Ages
- 14 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- According to the diagnostic criteria of HLH-04, the patients meet the diagnostic criteria of HLH;
- HLH patients with definite or highly suspected evidence of B-cell lymphoma; Or HLH patients whose bone marrow flow cytometry show an increased proportion of CD20-positive B cells;
- Age of 14-80 years old, both sexes;
- Predicted survival beyond 1 month;
- Baseline serum creatinine ≤1.5 times ULN; Fibrinogen could be corrected to ≥0.6g/L by infusion;
Key exclusion criteria (7 listed)
- Patients with known severe allergy to rituximab, zanubrutinib, or other BTK inhibitors;
- Severe active infections (including bacterial, viral or fungal infections) or uncontrolled co-infections;
- Severe organ dysfunction including NYHA class III-IV heart failure or severe arrhythmia; Liver function: ALT or AST >5 times the upper limit, or severe cirrhosis; Renal function: CrCl <30 mL/min or severe renal insufficiency;
- Combined with other malignant tumors and the expected survival time was less than 3 months;
- Have received other experimental drugs and had not completed the drug washout period;
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 |
|---|---|---|
| RituximabAlso: HALPRYZA375 mg/m², intravenously, once weekly for 4 weeks | Drug | intervention group |
| ZanubrutinibAlso: Brukinsa160 mg, orally, twice daily for 4 weeks as for rutuximab. | Drug | intervention group |
Primary outcome
response rate of HLH after 4 weeks of treatment
Time frame: after 4 weeks
RR will be evaluated according to the response evaluation criteria recommended by the International Histiocyte Society.
OS at week 8
Time frame: after 8 weeks
overall survival after 8 weeks of treatment
2 secondary outcomes
AE
Time frame: till the end of 4 weeks
OS
Time frame: at 4/8/12/24 weeks
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 8 Dec 2025.
- Individual participant dataSharing planned: Undecided
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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, doctor principal investigator
department of hematology, The First Affiliated Hospital of Soochow University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rituximab and Zanubrutinib in people with Hemophagocytic Lymphohistiocytosis and B Cell Lymphoma, run by The First Affiliated Hospital of Soochow University at 1 site in China.
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 10 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Xuefeng He, doctor (86-18914031640, hexuefeng@suda.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
response rate of HLH after 4 weeks of treatment (time frame: after 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Dec 2025.