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

First Affiliated Hospital of Ningbo University

Status and phase: Enrolling; Phase 2

Conditions: DLBCL; Diffuse Large B-Cell Lymphoma

Treatments: Drug: Drug therapy

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT06758037

2024-138A-02 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 70 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 70 years;
2. ECOG score 0-3;
3. Rated as "unfit" or "frail" on the simplified geriatric assessment (sGA);
4. Histologically confirmed CD20-positive diffuse large B-cell lymphoma [diagnostic criteria according to WHO 2016], excluding transformed type 2 DLBCL;
5. Previously untreated, newly diagnosed patients;
6. 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;
7. At least one measurable lesion;
8. Intolerance to standard CHOP chemotherapy regimen or unwillingness to receive chemotherapy;
9. Sufficient understanding and voluntary signing of the informed consent form.

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Patients with newly diagnosed, CD20+, elderly, chemotherapy-intolerant DLBCL

Experimental group

Description:

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

Treatment:

Drug: Drug therapy