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

Official title

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.

Overview

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.

Interventions

• Drug Drug 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

Primary outcome measures

• Complete response rate (CR) at the end of 6 cycles [Time frame: Each cycle consists of 21 days, with a total of 6 cycles.]

Eligibility criteria

Inclusion criteria

• 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 criteria

• 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.

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

• The First Affiliated Hospital of Ningbo University — Ningbo

Publications

• Poddubnaya IV, Alekseev SM, Kaplanov KD, Lukavetskyy LM, Rekhtman GB, Dolai TK, Attili VSS, Bermudez CD, Isaev AA, Chernyaeva EV, Ivanov RA. Proposed rituximab biosimilar BCD-020 versus reference rituximab for treatment of patients with indolent non-Hodgkin lymphomas: An international multicenter randomized trial. Hematol Oncol. 2020 Feb;38(1):67-73. doi: 10.1002/hon.2693. Epub 2020 Jan 13. PMID 31724191
• Shi Y, Song Y, Qin Y, Zhang Q, Han X, Hong X, Wang D, Li W, Zhang Y, Feng J, Yang J, Zhang H, Jin C, Yang Y, Hu J, Wang Z, Jin Z, Su H, Wang H, Yang H, Fu W, Zhang M, Zhang X, Chen Y, Ke X, Liu L, Yu D, Chen G, Wang X, Jin J, Sun T, Du X, Cheng Y, Yi P, Zhao X, Ma C, Cheng J, Chai K, Luk A, Liu E, Zhang X. A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma PMID 32299513

Identifiers

NCT: NCT06758037 · 2024-138A-02 · 2024-138A-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗