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

NCT ID: NCT06758037

Last Updated: 2025-03-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-15
• Study Completion Date: 2027-06-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: EXPERIMENTAL

Drug therapy

Intervention Type: 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

Interventions

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 qd For EZB: Chidamide 30mg biw

For N1-like and nonspecific types:

If EBV-positive: PD-1 monoclonal antibody 200mg Q3W

Intervention Type: DRUG

Other Intervention Names

Ocalivumab; Chidamide; PD-1 monoclonal antibody

Eligibility Criteria

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.

• Minimum Eligible Age: 70 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Ningbo University

NETWORK

Sponsor Role: lead

Responsible Party

Lixia Sheng

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital of Ningbo University

Ningbo, Zhejiang, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Sheng

Role: primary

fyyshenglixia@nbu.edu.cn

0574-87089203

References

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.

Reference Type: BACKGROUND

PMID: 31724191 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32299513 (View on PubMed)

Other Identifiers

2024-138A-02

Identifier Type: OTHER

Identifier Source: secondary_id

2024-138A-02

Identifier Type: -

Identifier Source: org_study_id