Polatuzumab, Rituximab and Orelabrutinib Combination Regimen (PRO) in the Treatment of Elderly Frail Patients with Treatment-naive Non-GCB DLBCL

A Prospective, Single-arm, Multicenter Clinical Study of Polatuzumab, Rituximab and Orelabrutinib Combination Regimen (PRO) in the Treatment of Elderly Patients with Frail Treatment-naive Non-germinal Center Subtype Diffuse Large B-cell Lymphoma

This prospective, single-arm, multicenter clinical study aims to enroll 30 frail elderly patients with Non-GCB DLBCL. This study is to evaluate the preliminary efficacy and safety of the combination of Polatuzumab, Rituximab, and orelabrutinib in this population. The primary endpoint is CR rate after induction therapy.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Drug: Polatuzumab vedotin; Drug: Rituximab; Drug: Orelabrutinib

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

Contacts and Locations

• Study Contact: Name: Wenyu Shi; Phone Number: +86 13515203737; Email: shiwenyu@hotmail.com

Study Locations

• China
  • Nanjing, China
    • Not yet recruiting
    • Jiangsu Province Hospital
    • Contact: Huayuan Zhu, PhD
  • Jiangsu
    • Nantong, Jiangsu, China, 226005
      • Recruiting
      • Affiliated Hospital of Nantong University
      • Contact: Wenyu Shi, Doctor; Phone Number: 13515203737; Email: shiwenyu@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with histopathologically confirmed DLBCL;

  • The sGA evaluation result of octogenarians or 60-79 years old is unfit or f RA il;

    • Non-germinal center (Non-GCB) type;

      • ECOG performance status score of 0-3 points; ⑤ No previous treatment for Lymphoma (unless glucocorticoid); 6 Radiographic Investigation to measurable disease, defined as the longest diameter with at least one Lymph node disorder > 1.5 cm, or at least one extranodal lesion > 1.0 cm in the longest diameter; ⑦ Adequate organ function;

        • Life expectancy ≥ 12 weeks; ⑨ Signed written informed consent.

Exclusion Criteria:

• Accompanied by uncontrolled cardiovascular and cerebrovascular diseases, Coagulopathy diseases, autoimmune diseases and severe Immunization diseases, etc.;

  • Laboratory abnormalities at screening (unless caused by Lymphoma) A) ANC < 1.5 x 109/L, PLT < 80 x 109/L b） Coagulation: INR greater than 1.5 x upper limit of normal; PT and APTT greater than 1.5 x upper limit of normal c） Liver function: ALT or AST 2 times higher than upper limit of normal, AKP and Bilirubin 1.5 times higher than upper limit of normal d） Renal function: Creatinine high 1.5 times the upper limit of normal, Creatinine clearance < 60 mL/min (estimated by C OC kcroft-Gault formula); ③ HIV Infection;

    • HbsAg positive patients should be HBV DNA negative before enrollment; in addition, if the patients are HBsAg negative but HBcAb positive (regardless of HBsAb status), HBV DNA detection is still required; if the results are positive, antiviral therapy is required, and HBV DNA negative before enrollment;

      • Requires continuous treatment with strong and moderate CYP3A inhibitors or CYP3A Induction agents. Patients who have taken strong and moderate CYP3A inhibitors or CYP3A Induction agents (or have taken these agents within 5 half-lives) within 7 days prior to the first dose of study drug should not be enrolled; ⑥ Inability to swallow capsules or suffering from diseases that seriously affect gastrointestinal function, such as Syndrome malabsorption, gastric or Small intestinal resection, symptomatic Inflammatory bowel disease or partial or complete Intestinal obstruction; ⑦ Other concurrent and uncontrolled medical conditions that, in the opinion of the investigators, would affect the patients' participation in the study, including patients with Psychosis or other patients known or suspected to be unable 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: PRO; The drugs involved in this trial include Polatuzumab, Rituximab, and orelabrutinib in 21-day cycles. The dose and administration method of the study drug were as follows: Polatuzumab: 1.8 mg/kg, IV, D1;; Rituximab: 375 mg/m2, IV, D1;; Orelabrutinib: 150 mg/time, qd, po, D1-21;	Drug: Polatuzumab vedotin; Polatuzumab: 1.8 mg/kg, IV Drip infusion, D1; Drug: Rituximab; Rituximab: 375 mg/m2, IV Drip infusion, D1; Drug: Orelabrutinib; Orelabrutinib: 150 mg/time, qd, po, D1-21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRR	Complete response rate (CRR) at the end of Induction treatment (6 cycles)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall response rate (ORR) at the end of Induction treatment (6 cycles)	6 months
2y-PFS rate	defined as the time from the start of treatment to the first documented Disease progression or Death; patients who have not experienced an event at the time of analysis will be censored at the date of the most recent disease assessment	24 months
OS	defined as the time from the start of treatment to the Death of death from any cause; patients who had not experienced an event at the time of analysis were censored at the date the patient was last known to be alive	24 months
EFS	defined as the time from the start of treatment until Disease progression/relapse, Death from any cause, or the start of next-line Lymphoma therapy (NALT); patients who have not experienced an event at the time of analysis will be censored at the date of the most recent disease assessment	24 months
Safety profile	defined as the incidence of Adverse event (AEs) that occurred from the date of the first dose of Carcinoma until 30 days after discontinuation of study drug or PD or initiation of new anti-safety therapy, whichever occurred first, and defined as all Adverse event that occurred after the patient received the study regimen; defined as the incidence of treatment-related AEs that were considered by the investigator to be related to Salvage therapy, Transplant, and consolidation therapy after the patient received the study regimen	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Potential predictive factors	defined as clinical and biological factors at baseline or during the treatment that might be associated with treatment efficacy and safety and was performed to screen out populations that would benefit more from this protocol.	24 months

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Nantong University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: July 23, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: DLBCL; elderly; PRO; frail; Non-GCB
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Immunoconjugates; Rituximab; Polatuzumab vedotin
• Other Study ID Numbers: JCLG-24-7

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in publication
• IPD Sharing Time Frame: starting 6 months after publication
• IPD Sharing Access Criteria: IPD could be shared by contacting the corresponding author via email after publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No