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

NCT06758037 | Recruiting Phase 2 DMC

• 1 other identifier: 2024-138A-02
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

DLBCL; Diffuse Large B-Cell Lymphoma

Keywords

DLBCL; genetic subtypes; Zebtorizumab; Lenalidomide; unfit

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CR) at the end of 6 cycles

  Complete response rate (CR) at the end of 6 cycles

  Each cycle consists of 21 days, with a total of 6 cycles.

Study Arms (1)

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

EXPERIMENTAL

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

Drug: Drug therapy

Interventions

Drug therapy DRUG

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

Also known as: Ocalivumab, Chidamide, PD-1 monoclonal antibody

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

Eligibility Criteria

• Age: 70 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Ningbo University: lead

Study Sites (1)

The First Affiliated Hospital of Ningbo University

Ningbo, Zhejiang, 3150101, China

RECRUITING

Related Publications (2)

• 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 BACKGROUND

• 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. J Hematol Oncol. 2020 Apr 16;13(1):38. doi: 10.1186/s13045-020-00871-9.

  PMID: 32299513 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Drug Therapy; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; spartalizumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: January 3, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: March 18, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)