Orelabrutinib Combined With Standard Immunochemotherapy With or Without Autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT) for Newly Diagnosed Diffuse Large B-cell Lymphoma (DLBCL)

A Prospective, Phase II Clinical Study Protocol of Orelabrutinib Combined With Standard Immunochemotherapy With or Without Autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT) for Newly Diagnosed Diffuse Large B-cell Lymphoma (DLBCL)

This study is a prospective, open-label, multicenter study in previously untreated participants with CD20-positive DLBCL. Orelabrutinib combined with standard immunochemotherapy with or without autologous hematopoietic stem cell transplantation (auto-HSCT) for newly diagnosed diffuse large B-cell lymphoma (DLBCL). The primary objective is to explore the 1-year progression-free survival (PFS) of orelabrutinib combined with standard immunochemotherapy with or without auto-HSCT in newly diagnosed DLBCL.

Diffuse large B-cell lymphoma (DLBCL), as the most common type of adult lymphoma, accounts for 35%-40% of non-Hodgkin lymphoma (NHL) and is characterized by high heterogeneity. This study is a prospective, open-label, multicenter study in previously untreated participants with CD20-positive DLBCL. In the induction phase, patients receive 4 cycles of orelabrutinib combined with standard chemotherapy. For transplant-eligible patients, based on response assessment after 4 cycles, those achieving PR or CR proceed to auto-HSCT, followed by either 6 cycles of orelabrutinib maintenance or no maintenance based on patient preference. For transplant-ineligible patients, based on response assessment after 4 cycles, those achieving PR or CR receive an additional 2-4 cycles of orelabrutinib combination therapy. Depending on the patient's performance status, each cycle lasts 21-28 days. The primary objective is to explore the 1-year progression-free survival (PFS) of orelabrutinib combined with standard immunochemotherapy with or without auto-HSCT in newly diagnosed DLBCL.

Inclusion Criteria:

• Signed informed consent;

  • Age 18-80 years at the time of signing informed consent, and willingness to comply with the study protocol procedures;

    • Pathologically confirmed CD20-positive DLBCL;

      ④ IPI score of 2-5;

      ⑤ ECOG performance status of 0-2;

      ⑥ Life expectancy ≥12 months;

      ⑦ Left ventricular ejection fraction (LVEF) ≥50% as assessed by multigated acquisition (MUGA) scan or echocardiography (ECHO);

      • Adequate hematologic function (unless due to underlying disease, e.g., extensive bone marrow involvement, or hypersplenism secondary to splenic involvement attributed to DLBCL as determined by the investigator; transfusion of blood products is permitted), defined as follows:

        1. Hemoglobin ≥90 g/L within 7 days prior to enrollment without packed red blood cell transfusion;

        2. Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L;

        3. Platelet count ≥75 × 10⁹/L.

           ⑨ Adequate organ function.

           Exclusion Criteria:

• Presence of uncontrolled cardiovascular or cerebrovascular disease, coagulation disorders, autoimmune diseases, severe infectious diseases, etc.;

  • Abnormal laboratory values at screening (unless attributable to lymphoma):

    1. Coagulation function: INR > 1.5× the upper limit of normal (ULN); PT and APTT > 1.5× ULN;

    2. Liver function: ALT or AST > 2× ULN; ALP and bilirubin > 1.5× ULN;

    3. Renal function: Creatinine > 1.5× ULN; creatinine clearance < 60 mL/min (estimated by the Cockcroft-Gault formula);

       ③ HIV-infected patients;

       ④ For HBsAg-positive patients, HBV DNA must be negative prior to enrollment. In addition, if a patient is HBsAg-negative but HBcAb-positive (regardless of HBsAb status), HBV DNA testing is still required. If the result is positive, antiviral therapy is needed, and HBV DNA must be negative prior to enrollment;

       ⑤ Requiring continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers. Patients who have taken strong or moderate CYP3A inhibitors or CYP3A inducers within 7 days prior to the first dose of study drug (or have not completed at least 5 half-lives since the last dose) are not eligible for enrollment;

       • Inability to swallow capsules or presence of gastrointestinal conditions that significantly affect gastrointestinal function, such as malabsorption syndrome, gastric or small bowel resection, symptomatic inflammatory bowel disease, or partial or complete intestinal obstruction;

         • Other concurrent and uncontrolled medical conditions that, in the investigator's opinion, may affect the patient's participation in the study, including patients with psychiatric disorders or other known or suspected inability to fully comply with the study protocol.