The Efficacy and Safety of Pola-ZR2 Versus ZR2 in the Treatment of Old Patients With de Novo Diffuse Large B-cell Lymphoma

The Efficacy and Safety of Pola-ZR2 (Polatuzumab Vedotin, Zanubrutinib, Rituximab and Lenalidomide) Versus ZR2 (Zanubrutinib, Rituximab and Lenalidomide) in the Treatment of Old Patients With de Novo Diffuse Large B-cell Lymphoma: A Multicenter, Prospective, Randomized, Open-label, Controlled Trial

A multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of Pola-ZR2 (polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide) versus ZR2 (zanubrutinib, rituximab and lenalidomide) in the treatment of old patients with de novo diffuse large B-cell lymphoma

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide; Drug: zanubrutinib, rituximab and lenalidomide

Detailed Description

This study will evaluate the efficacy and safety of Pola-ZR2 versus ZR2 in the treatment of elderly de novo diffuse large B-cell lymphoma patients. Subjects will be randomly assigned 1:1 to Pola-ZR2 or ZR2 regimen. The stratification will be performed according to international prognostic index (2-3 / 4-5).

Patients in Pola-ZR2 group will receive 6 cycles of polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle, zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days. 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.

Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Weili Zhao; Phone Number: 610707 +862164370045; Email: zwl_trial@163.com
• Study Contact Backup: Name: Li Wang; Phone Number: 610707 +862164370045; Email: wl_wangdong@126.com

Study Locations

• China
  • Shanghai, China, 200025
    • Recruiting
    • Shanghai Institute of Hematology, Rui-Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
    • Contact: Weili Zhao; Phone Number: 610707 +862164370045; Email: zwl_trial@163.com
    • Contact: Pengpeng Xu; Phone Number: 610707 +862164370045; Email: pengpeng_xu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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)
• Aged ≥ 80 years old or aged 70-79 with comprehensive geriatric assessment stratified as unfit or frail
• International prognostic index score 2 to 5
• 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)
• Able to swallow capsules
• 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)

Exclusion Criteria:

Presence of any of the following criteria will exclude a patient from enrollment:

• Uncontrolled 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 ALT or AST is 2 times higher than the upper limits of normal (ULN), serum 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).

• uncontrollable or significant cardiovascular diseases, including but not limited to: Left ventricular ejection fraction<50% Cardiomyopathy, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy QTc prolongation with clinical significance, QTc interval>470ms (females) or 480ms (males), type 2 second-degree atrioventricular block or third-degree atrioventricular block
• 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
• Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
• HIV-infected patients
• History of stroke or intracranial hemorrhage within 6 months prior to start of therapy
• Other medical conditions determined by the researchers that may affect the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pola-ZR2; six courses of polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy	Drug: polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide; Drug: Polatuzumab vedotin, Zanubrutinib, Lenalidomide and Rituximab (Pola-ZR2) Induction therapy: The Pola-ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles. Dosage: Polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle; Zanubrutinib, 160 mg bid, po, day 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1. Maintenance therapy: Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.
Active Comparator: ZR2; six courses of zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy	Drug: zanubrutinib, rituximab and lenalidomide; Drug: Zanubrutinib, Lenalidomide and Rituximab (ZR2) Induction therapy: The ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles. Dosage: Zanubrutinib, 160 mg bid, po, day 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1. Maintenance therapy: Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year PFS rate	up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Overall survival	Overall survival was defined as the time from the date of randomization to the date of death from any cause.	Baseline up to data cut-off (up to approximately 2 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)	Quality of Life will be assessed by EORTC QLQ-C30 (Verison 3.0).	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)	Quality of Life will be assessed by EORTC QLQ-ELD14.	Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
Percentage of Participants Achieving Meaningful Improvement in Functional Assessment of Cancer Therapy-Lymphoma Lymphoma Subscale (FACT-Lym LymS)	Quality of Life will be assessed by FACT-Lym LymS.	Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
2-year OS rate	2-year OS rate	Baseline up to data cut-off (up to approximately 2 years)
Complete response rate	Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.	End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
Overall response rate	Percentage of participants with complete or partial response was determined on the basis of investigator assessments according to 2014 Lugano criteria.	End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	From enrollment to study completion, a maximum of 5 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2024
• Primary Completion (Estimated): August 10, 2028
• Study Completion (Estimated): August 10, 2029

Study Registration Dates

• First Submitted: July 7, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 26, 2024

Study Record Updates

• Last Update Posted (Estimated): August 5, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: lenalidomide; rituximab; old patients; zanubrutinib; frail; polatuzumab vedotin; diffuse large B-cell lymphoma; unfit
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Immunoconjugates; Tyrosine Kinase Inhibitors; Lenalidomide; Rituximab; Zanubrutinib; Polatuzumab vedotin
• Other Study ID Numbers: POTENT STUDY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No