Zanubrutinib plus rituximab for secondary HLH linked to B‑cell lymphoma

The Study of Zanubrutinib Combined With Rituximab in the Treatment of Secondary Hemophagocytic Lymphohistiocytosis in B-cell Lymphoma

This test tries zanubrutinib together with rituximab (plus short steroids and ruxolitinib, with emapalumab if needed) to treat people who have secondary HLH caused by B‑cell lymphoma.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 14 Years to 80 Years
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: rituximab, zanubrutinib, emapalumab, Ruxolitinib, prednisone, rutuximab
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07270835 on ClinicalTrials.gov

What this trial studies

This single-center phase 4 program gives rituximab 375 mg/m² IV once weekly for four weeks combined with zanubrutinib 160 mg orally twice daily, alongside short-course prednisone and ruxolitinib, with emapalumab added if clinically indicated. Doses may be adjusted or extended based on response and tolerability, and zanubrutinib dosing is modified for interactions with strong CYP3A inhibitors or inducers. Treatment is paused or dose‑reduced for grade ≥3 hematologic or intolerable non‑hematologic toxicities until recovery. Eligible patients are aged 14–80 with HLH related to definite or suspected B‑cell lymphoma or increased bone‑marrow CD20+ B cells and must have adequate organ function and no uncontrolled infections.

Who should consider this trial

Good fit: Ideal candidates are people aged 14–80 with secondary HLH clearly or strongly linked to B‑cell lymphoma (or increased CD20+ marrow cells), with adequate organ function, no uncontrolled infections, and expected survival beyond one month.

Not a fit: Patients with primary (genetic) HLH, HLH from non‑B‑cell causes, uncontrolled severe infections, very poor organ function, or active high‑titer viral hepatitis are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could help control the HLH cytokine storm while treating the underlying B‑cell lymphoma, potentially improving symptom control and survival.

How similar studies have performed: Rituximab is an established therapy for B‑cell–driven HLH, but combining zanubrutinib with rituximab for secondary HLH is a relatively new approach with limited published evidence to date.

Eligibility criteria

Inclusion Criteria:

* 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;
* 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.

Exclusion Criteria:

* 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.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Principal investigator: Xuefeng He, doctor — department of hematology, The First Affiliated Hospital of Soochow University
• Study coordinator: Xuefeng He, doctor

Conditions Hemophagocytic Lymphohistiocytosis; B Cell Lymphoma