The Efficacy and Safety of ZR2 Versus R-miniCHOP in the Treatment of Unfit or Frail de Novo Diffuse Large B-cell Lymphoma Patients Aged Older Than or Equal to 70 Years

NCT05179733 | Unknown Phase 3 DMC

• 1 other identifier: NHL-014
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

A multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of zanubrutinib, rituximab and lenalidomide (ZR2) versus rituximab combined with low-dose CHOP (R-miniCHOP) in the treatment of unfit or frail de novo diffuse large B-cell lymphoma patients aged older than or equal to 70 years

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

Diffuse Large B-Cell Lymphoma; Elderly patients; Zanubrutinib; Lenalidomide; Rituximab; R-miniCHOP

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression-free survival was defined as the time from the date of randomization until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.

  Baseline up to data cut-off (up to approximately 2 years)

Secondary Outcomes (6)

• Complete response rate

  At the end of Cycle 6 (each cycle is 21 days)

• Overall survival

  Baseline up to data cut-off (up to approximately 2 years)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  From enrollment to study completion, a maximum of 4 years

• Percentage of Participants Achieving Meaningful Improvement in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)

  Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion

• Percentage of Participants Achieving Meaningful Improvement in EORTC QLQ-ELD14 (Elderly Module)

  Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion

Study Arms (2)

ZR2

EXPERIMENTAL

six courses of zanubrutinib, rituximab and lenalidomide

Drug: six courses of zanubrutinib, rituximab and lenalidomide

R-miniCHOP

ACTIVE COMPARATOR

six courses of rituximab combined with low-dose CHOP

Drug: six courses of rituximab combined with low-dose CHOP

Interventions

six courses of zanubrutinib, rituximab and lenalidomide DRUG

Patients in ZR2 group will receive 6 cycles of zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days.

ZR2

six courses of rituximab combined with low-dose CHOP DRUG

Patients in R-miniCHOP group will receive rituximab 375 mg/m² on day 1, cyclophosphamide 400 mg/m², doxorubicin 25 mg/m², and vincristine 1 mg on day 2, and prednisone 40 mg/m² on days 2-6, every 21 days.

R-miniCHOP

Eligibility Criteria

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

You may qualify if:

• Patients must satisfy all of the following criteria to be enrolled in the study:
• Histologically-confirmed diffuse large B-cell lymphoma (without central nervous system involvement)
• Eastern Cooperative Oncology Group performance status 0-3
• Aged ≥ 80 years old or aged 70-79 with comprehensive geriatric assessment stratified as unfit or frail
• International normalized ratio and activated partial thromboplastin time are both 1.5 times lower than the upper limits of normal (ULN).
• At least 1 measurable site of disease (defined as lymph nodes with the long diameters longer than 1.5cm, or extra-nodal sites with the long diameters longer than 1.0cm; meanwhile, any lesion site with at least 2 measurable vertical diameters)
• Life expectancy of at least 3 months determined by researchers
• The patient or his or her legal representative must provide written informed consent prior to any special examination or procedure for the research.
• Anti-lymphoma drugs have not been used before (except glucocorticoids).

You may not qualify if:

• Presence of any of the following criteria will exclude a patient from enrollment:
• Uncontrolled cardio- and cerebro-vascular disease, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases
• Laboratory measures meet the following criteria at screening (unless caused by lymphoma):
• Neutrophils\<1.5×10\^9/L
• Platelets\<80×10\^9/L (Platelets\<50×10\^9/L in case of bone marrow involvement)
• ALT or AST is 2 times higher than the upper limits of normal (ULN), AKP and bilirubin are 1.5 times higher than the ULN.
• Creatinine is 1.5 times higher than the ULN or eGFR is lower than 40ml/min/1.73m\^2 (according to Cockcroft-Gault Equation or MDRD Equation).
• HIV-infected patients
• Left ventricular ejection fraction\<50%
• Patients with HbsAg positive are required to have HBV DNA\<1.0×10\^3 IU/ml before entering the group. In addition, if the patient is HBsAg negative but HBcAb positive (regardless of HBsAb status), HBV DNA test is also required, and HBV DNA\<1.0×10\^3 IU/ml is required before entering the group.
• Other anti-tumor treatments (lymphoma or other types of tumors) are currently in progress.
• Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
• Require treatment with strong/moderate CYP3A inhibitors or inducers.
• History of stroke or intracranial hemorrhage within 6 months prior to start of therapy
• Inability to swallow capsules or presence of diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, post-bariatric surgery, inflammatory bowel disease and complete or incomplete intestinal obstruction

Sponsors & Collaborators

• Ruijin Hospital: lead
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• Ningbo No. 1 Hospital: collaborator
• National Naval Medical Center: collaborator
• Shanghai Fengxian District Central Hospital: collaborator
• YANCHENG NO.1 PEOPLE'S HOSPITAL: collaborator
• The First Affiliated Hospital of Nanchang University: collaborator
• Affiliated Hospital of Nantong University: collaborator
• Sir Run Run Shaw Hospital: collaborator
• Northern Jiangsu People's Hospital: collaborator
• The First People's Hospital of Changde City: collaborator
• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: collaborator
• Changzhou No.2 People's Hospital: collaborator
• The Affiliated Hospital of Xuzhou Medical University: collaborator
• Huai'an First People's Hospital: collaborator
• Taizhou Hospital: collaborator
• The First People's Hospital of Kunshan: collaborator
• First Affiliated Hospital of Fujian Medical University: collaborator
• Huadong Hospital: collaborator
• Henan Provincial People's Hospital: collaborator
• First Hospital of China Medical University: collaborator
• Shandong Provincial Hospital: collaborator
• HARBIN THE FIRST HOSPITAL: collaborator
• The First Hospital of Jilin University: collaborator
• Hunan Cancer Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• THE FIRST AFFILIATED HOSPITAL: collaborator
• The Second Affiliated Hospital of Dalian Medical University: collaborator
• SUZHOU HONGCI HEMATOLOGY HOSPITAL: collaborator

Study Sites (1)

Ruijin Hospital

Shanghai, Shanghai Municipality, 200020, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Lenalidomide

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Weili ZHAO

CONTACT

+862164370045; zwl_trial@163.com

Pengpeng XU

CONTACT

+862164370045; pengpeng_xu@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: First Deputy Director, Hematology Department

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: January 5, 2022
• Study Start: March 2, 2022
• Primary Completion: December 25, 2025
• Study Completion: December 25, 2025
• Last Updated: May 23, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)