RecruitingPhase 2NCT06758037

Clinical Study of HiR+X Therapy for Newly Diagnosed Elderly Patients with DLBCL Intolerant to Chemotherapy

A Single-arm, Multicenter Phase II Clinical Study of HiR+X Therapy for Newly Diagnosed Diffuse Large B-cell Lymphoma (DLBCL) in Elderly Patients Intolerant to Chemotherapy, Guided by Molecular Subtyping and Clinical Characteristics.

Sponsor

First Affiliated Hospital of Ningbo University

Enrollment

50 participants

Start Date

Jan 15, 2025

Study Type

INTERVENTIONAL

Conditions

Diffuse Large B Cell Lymphoma DLBCL

Summary

To explore the application of HiR (Zebtorizumab, Lenalidomide) + X (targeted drug) guided by NGS molecular typing, the aim is to assess the therapeutic efficacy and safety in newly diagnosed unfit or frail elderly patients with DLBCL aged ≥70 years, and to investigate the genetic subtypes that may benefit from HiR-X.

Eligibility

Min Age: 70 YearsMax Age: 100 Years

Inclusion Criteria9

Age ≥ 70 years;
ECOG score 0-3;
Rated as "unfit" or "frail" on the simplified geriatric assessment (sGA);
Histologically confirmed CD20-positive diffuse large B-cell lymphoma \[diagnostic criteria according to WHO 2016\], excluding transformed type 2 DLBCL;
Previously untreated, newly diagnosed patients;
Cardiac, hepatic, and renal function: creatinine \< 2 times the upper limit of normal (ULN); ALT (alanine aminotransferase) / AST (aspartate aminotransferase) \< 2.5 x ULN; total bilirubin \< 2 x ULN;
At least one measurable lesion;
Intolerance to standard CHOP chemotherapy regimen or unwillingness to receive chemotherapy;
Sufficient understanding and voluntary signing of the informed consent form.

Exclusion Criteria7

Patients with central nervous system involvement at the onset of the disease;
Known human immunodeficiency virus (HIV) infection;
Pregnant or lactating women;
Other tumors requiring treatment;
Uncontrolled active infection;
Active hepatitis with HBV-DNA copy number unable to be controlled within 2000/mL despite antiviral treatment;
Individuals who cannot understand, comply with the study protocol, or sign the informed consent form.

Interventions

DRUGDrug therapy

All patients will receive one cycle of HiR (Zebtorizumab, Lenalidomide) induction therapy. On the first day of enrollment, tissue NGS and peripheral blood ctDNA will be submitted for testing. For the remaining six cycles, the added drug (X) will be determined based on the NGS molecular typing results. Please refer to the grouping scheme for details. HiR+X Dosing Scheme: Hi: Zebtorizumab 375mg/m², d1; R: Lenalidomide 10-25mg d1-10 (maximum tolerated dose) X: For MCD/BN2/TP53: Ocalivumab 150mg qd For EZB: Chidamide 30mg biw For N1-like and nonspecific types: If EBV-positive: PD-1 monoclonal antibody 200mg Q3W