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

NCT06522555 | Recruiting Phase 3 DMC

• 1 other identifier: POTENT STUDY
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

diffuse large B-cell lymphoma; polatuzumab vedotin; zanubrutinib; lenalidomide; rituximab; old patients; unfit; frail

Outcome Measures

Primary Outcomes (1)

• 2-year PFS rate

  up to approximately 2 years

Secondary Outcomes (9)

• Progression free survival

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

• 2-year OS rate

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

• Overall survival

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

• Complete response rate

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]

• Overall response rate

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]

Study Arms (2)

Pola-ZR2

EXPERIMENTAL

six courses of polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy

Drug: polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide

ZR2

ACTIVE COMPARATOR

six courses of zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy

Drug: zanubrutinib, rituximab and lenalidomide

Interventions

polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide DRUG

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.

Pola-ZR2

zanubrutinib, rituximab and lenalidomide DRUG

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.

ZR2

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)
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Shanghai Institute of Hematology, Rui-Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, 200025, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

polatuzumab vedotin; zanubrutinib; 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

Li Wang

CONTACT

+862164370045; wl_wangdong@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: Professor and Director, Shanghai Institute of Hematology

Study Record Dates

• First Submitted: July 7, 2024
• First Posted: July 26, 2024
• Study Start: July 29, 2024
• Primary Completion (Estimated): August 10, 2028
• Study Completion (Estimated): August 10, 2029
• Last Updated: August 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)