Pirtobrutinib+Pola-R-CHP for Newly Diagnosed Non-GCB DLBCL

Official title

A Prospective, Multicenter Clinical Study of Pirtobrutinib Combined With Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin and Prednisone (Pola-R-CHP) for Newly Diagnosed Non-GCB Diffuse Large B-Cell Lymphoma (DLBCL)

Overview

This is a single-arm, open-label, multicenter clinical study evaluating the efficacy and safety of pirtobrutinib combined with Pola-R-CHP in previously untreated Non-GCB DLBCL. PET/CT assessment will be performed after 3 cycles of combination therapy. Patients achieving CR/PR will continue treatment for another 3 cycles, while those with PD/SD will be discontinued from the study. Patients achieving CR/PR after 6 cycles of treatment will undergo follow-up with PET/CT or contrast-enhanced CT every 3 months during the first year and every 6 months thereafter, until disease progression, death, withdrawal of informed consent, or study completion, whichever occurs first.

Interventions

• Drug Pirtobrutinib+Pola-R-CHP
  Pirtobrutinib 200 mg once daily Polatuzumab vedotin 1.8 mg/kg intravenously on Day 1 Rituximab 375 mg/m² on Day 1 Cyclophosphamide 750 mg/m² on Day 1 Doxorubicin 50 mg/m² on Day 1 Prednisone 100 mg on Days 1 to 5 Each cycle lasts 21 days. PET/CT evaluation is conducted after 3 treatment cycles. Subjects who attain CR or PR will receive an additional 3 cycles of therapy. Subjects with PD or SD will be withdrawn from the study. Subjects who do not achieve CR or PR upon completion of 6 cycles will

Primary outcome measures

• 2-year progression-free survival (PFS) rate [Time frame: 2 years]

Secondary outcome measures (4)

• Objective Response Rate (ORR) after 6 cycles of induction therapy [Time frame: week 18，at the end of 6 cycles of induction therapy(each cycle is 21 days)]
• Complete Response Rate (CRR) after 6 cycles of induction therapy [Time frame: week 18, at the end of 6 cycles of induction therapy(each cycle is 21 days)]
• Overall Survival(OS) [Time frame: up to 4 years]
• Number of participants with treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0 [Time frame: up to 4 years]

Eligibility criteria

Inclusion criteria

• Histologically confirmed Non-GCB DLBCL (per 2016 WHO diagnostic criteria);
• Whole-body PET/CT performed within 28 days prior to study enrollment demonstrating at least one measurable lesion (per 2014 Lugano criteria);
• Age 18-65 years, with expected survival >3 months;
• No prior anti-lymphoma treatment;
• Signed written informed consent and ability to comply with protocol-required visits and procedures;
• ECOG performance status 0-2;
• Adequate organ and bone marrow function, defined as follows:

• Hematology: Absolute neutrophil count (ANC) ≥1×10⁹/L, platelet count (PLT) ≥50×10⁹/L, hemoglobin (HGB) ≥8.0 g/dL; no granulocyte colony-stimulating factor, platelet transfusion, or red blood cell transfusion within 7 days prior to testing;
• Hepatic function: Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN;
• Renal function: Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CCR) ≥50 mL/min;
• Cardiac function: NYHA Class III or below; left ventricular ejection fraction ≥50% by echocardiography;
• Coagulation: International normalized ratio (INR) ≤1.5×ULN, activated partial thromboplastin time (APTT) ≤ULN +10s, and prothrombin time (PT) ≤ULN +3s;
• Women of childbearing potential or male subjects with partners of childbearing potential must use effective contraception throughout the treatment period and for 90 days after the last dose.

Exclusion criteria

• Central nervous system involvement;
• History of hypersensitivity to the study drug, drugs of the same class, or excipients;
• Concurrent malignancy requiring treatment or intervention;
• Major surgery within 4 weeks prior to treatment (excluding vascular access catheter placement or biopsy);
• Presence of any life-threatening disease, medical condition, or organ system dysfunction that, in the investigator's opinion, may affect patient safety or compliance with study procedures;
• Uncontrolled cardiac symptoms or disease, including: i. NYHA Class II or higher heart failure; ii. Unstable angina; iii. Myocardial infarction within 1 year; iv. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
• Active bleeding;
• Active, uncontrolled systemic bacterial, viral, fungal, or parasitic infection (excluding onychomycosis), or other clinically significant active disease process that, in the investigator's opinion, renders the patient unsuitable for clinical trial participation;
• Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome;
• Exclusion of patients with active chronic hepatitis B or active hepatitis C. Patients with positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody at screening must undergo further HBV-DNA and HCV-RNA testing. Patients with stable hepatitis B (HBV-DNA <2500 copies/mL or 500 IU/mL) on antiviral therapy and cured hepatitis C patients (below the limit of detection) may be enrolled;
• Definitive history of neurological or psychiatric disorder, including epilepsy or dementia;
• Pregnant or lactating women;
• Receipt of other investigational agents within 1 month prior to first dose;
• Any other factors that, in the investigator's opinion, may affect the evaluation of efficacy or safety in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Jiangsu Province Hospital The First Affiliated Hospital with Nanjing Medical University — Nanjing

Identifiers

NCT: NCT07744724 · 2026CELH025-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗