Orelabrutinib plus Pola‑R‑CHP for untreated non‑GCB diffuse large B‑cell lymphoma

A Prospective, Single-Arm, Multicenter Clinical Study of Orelabrutinib Combined With Pola-R-CHP Regimen for the Treatment of Untreated Non-GCB Diffuse Large B-Cell Lymphoma

This trial tests whether adding orelabrutinib to the Pola‑R‑CHP chemotherapy improves responses in adults with newly diagnosed non‑GCB diffuse large B‑cell lymphoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (other)
• Drugs / interventions: orelabrutinib, rituximab
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07078500 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial gives treatment‑naive adults with non‑GCB DLBCL six 21‑day cycles of orelabrutinib combined with the Pola‑R‑CHP regimen and performs an interim efficacy and safety assessment after cycle six. Patients achieving a complete or partial response then receive two additional cycles of orelabrutinib with rituximab for a total of eight induction cycles, followed by a final evaluation. Eligible participants are 18–80 years old with measurable disease, ECOG 0–2 and adequate organ function, while those with CNS involvement or certain lymphoma subtypes are excluded. The combination of a BTK inhibitor with the Pola‑R‑CHP backbone is novel and the trial will provide initial safety and efficacy data for this approach.

Who should consider this trial

Good fit: Adults aged 18–80 with newly diagnosed, treatment‑naive non‑GCB DLBCL, at least one measurable lesion, ECOG 0–2, and adequate laboratory values who can attend the Zhejiang clinic are ideal candidates.

Not a fit: Patients with CNS or leptomeningeal involvement, transformed lymphoma, primary mediastinal or Burkitt subtypes, significant baseline organ dysfunction, or prior anti‑tumor therapy are unlikely to benefit or to be eligible.

Why it matters

Potential benefit: If successful, this combination could raise response rates and improve outcomes for patients with poor‑prognosis non‑GCB DLBCL compared with current Pola‑R‑CHP therapy.

How similar studies have performed: BTK inhibitors have shown activity when combined with R‑CHOP‑like regimens in similar populations, but combining a BTK inhibitor with Pola‑R‑CHP is novel and has not been reported.

Eligibility criteria

Inclusion Criteria:

1. Age 18 to 80 years old.
2. Diffuse large B-cell lymphoma (DLBCL) confirmed by tumor tissue pathology, with at least one measurable lesion.
3. Non-GCB.
4. No prior anti-tumor treatment.
5. ECOG score of 0-2.
6. Life expectancy of ≥6 months.
7. Voluntary written informed consent.

Exclusion Criteria:

1. Lymphoma involving the central nervous system or leptomeningeal metastasis.
2. Transformed lymphoma, that is, transformed from other types of lymphoma, such as follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, or small B-cell lymphoma.
3. Primary mediastinal large B-cell lymphoma.
4. Burkitt lymphoma.
5. Laboratory values at screening (unless due to lymphoma):

   1. Neutrophils \<1.5×10⁹/L;
   2. Platelets \<75×10⁹/L;
   3. ALT or AST more than 2 times the upper limit of normal, ALP and bilirubin more than 1.5 times the upper limit of normal;
   4. Creatinine level more than 1.5 times the upper limit of normal.
6. Patients with psychiatric disorders or other known or suspected inability to fully comply with the study protocol.
7. Pregnant or breastfeeding women.
8. Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C virus infection (positive result by polymerase chain reaction \[PCR\]). If the patient tests positive for HbsAg, HBV DNA testing is required. If HBV DNA \<10³ IU/ml, the patient may be enrolled. If the patient tests negative for HbsAg but positive for HBcAb (regardless of HBsAb status), HBV DNA testing is also required. If HBV DNA \<10³ IU/ml, the patient may be enrolled. If the patient tests positive for HCV antibody, HCV RNA is detected by PCR. If positive, the patient meets the exclusion criteria.
9. Need for continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers.
10. Inability to swallow capsules or significant gastrointestinal disorders, such as malabsorption syndrome, bariatric surgery, inflammatory bowel disease, or partial or complete intestinal obstruction.
11. Other concurrent and uncontrolled medical conditions that the investigator believes will affect the patient's participation in the study.

Where this trial is running

Hangzhou, Zhejiang

• Second Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: hui Liu

Conditions: Diffuse Large B-Cell Lymphoma