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.

Study Overview

• Status: Recruiting
• Conditions: DLBCL - Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Drug: Orelabrutinib combined with standard immunochemotherapy with or without auto-HSCT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Feng Zhu; Phone Number: 0516-85806985; Email: frankfeng_2004@126.com

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Feng Zhu; Phone Number: 0516-85806985; Email: frankfeng_2004@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Orelabrutinib combined with standard immunochemotherapy with or without auto-HSCT; 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.

Drug: Orelabrutinib combined with standard immunochemotherapy with or without auto-HSCT; 1+2.1 or 2.2 ±3 1. Orelabrutinib: 150 mg once daily, orally, Days 1-28 2.1 Pola-R-CHP Regimen: Polatuzumab vedotin: 1.8 mg/kg, intravenous infusion, Day 1 Rituximab: 375 mg/m², intravenous infusion, Day 1 Cyclophosphamide: 750 mg/m², intravenous administration, Day 2 Doxorubicin: 50 mg/m², intravenous administration or per institutional guidelines, Day 2 Prednisone: 100 mg/day, orally, Days 2-6 2.2. R-CHOP Regimen: Rituximab: 375 mg/m², intravenous infusion, Day 0 Cyclophosphamide: 750 mg/m², intravenous administration, Day 1 Doxorubicin: 40-50 mg/m², intravenous administration or per institutional guidelines, Day 1 Vincristine: 1.4 mg/m², intravenous administration, Day 1 (maximum dose 2 mg) OR Vindesine: 4 mg, intravenous administration, Day 1 Prednisone: 100 mg/day, orally, Days 1-5 3. auto-HSCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year Progression free survival (PFS)	PFS is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.	From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR (Objective Response Rate)	ORR is defined as the proportion of patients with a response of CR or PR	At the end of Consolidation therapy (up to 8 cycles, each cycle is 21-28 days )
CRR (Complete Response Rate)	CRR is defined as the proportion of patients with a best response of CR	At the end of Consolidation therapy (up to 8 cycles, each cycle is 21-28 days)
2-year Progression free survival (PFS)	PFS is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.	From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
2-year overall survival (OS)	Overall survival is defined as the period from the induction registration to death from any cause. Patients who have not died until the time of the analysis will be censored at their last contact date.	From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
The occurrence of adverse events and serious adverse events		At the end of whole theray (through study completion, an average of 1 year)

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: DLBCL; Orelabrutinib; auto-HSCT
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Lymphatic Diseases; Histiocytic Disorders, Malignant; Histiocytosis; Hemic and Lymphatic Diseases; Dendritic Cell Sarcoma, Interdigitating
• Other Study ID Numbers: XYFY2026-001-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No