The Efficacy and Safety of Pola-ZR-Glo in Older Treatment-naive Patients With LBCL

Official title

The Efficacy and Safety of Pola-ZR-Glo (Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Glofitamab) Regimen in Older Treatment-naive Patients With Large B-cell Lymphoma (LBCL)

Overview

This is a prospective, single-center, open-label, single-arm clinical study designed to evaluate the efficacy and safety of Pola-ZR-Glo (Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Glofitamab) regimen in older treatment-naive patients with large B-cell lymphoma.

Interventions

• Drug Pola-ZR-Glo (Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Glofitamab) regimen
  Pola-ZR-Glo (Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Glofitamab) 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 12 cycles. Dosage: Polatuzumab vedotin (1.8 mg/kg) will be administered intravenously on Day 2 of Cycle 1 and on Day 1 of Cycles 2-6 (each Q3W). Zanubrutinib (160mg bid p.o.) will be administered from D1 to D21 through Cycles 1-6 Q3W. Lenalidomide (25mg qd p.o.) will be administered fro

Primary outcome measures

• Progression free survival [Time frame: Baseline up to data cut-off (up to approximately 2 years)]

Secondary outcome measures (7)

• Event-free survival [Time frame: Baseline up to data cut-off (up to approximately 2 years)]
• Complete response rate [Time frame: At the end of Cycle 3, 6 and at the end of treatment (each cycle is 21 days)]
• Objective response rate [Time frame: At the end of Cycle 3, 6 and at the end of treatment (each cycle is 21 days)]
• Overall Survival [Time frame: Baseline up to data cut-off (up to approximately 2 years)]
• DoR [Time frame: From documentation of CR/PR until relapse/progression or death due to any reason without documented relapse, whichever came first, assessed up to 32 months.]
• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0 [Time frame: From enrollment to study completion, a maximum of 4 years]
• Patient reported outcome [Time frame: Day 1 of Cycles 1, 4 and 7 (Cycle length=21 days); 30 days after treatment completion]

Eligibility criteria

Inclusion criteria

Patients must satisfy all of the following criteria to be enrolled in the study:

• Histologically-confirmed large B-cell lymphoma (without central nervous system involvement)
• Aged ≥ 70 years old with comprehensive geriatric assessment stratified as unfit or frail, or those who decline immunochemotherapy.
• Eastern Cooperative Oncology Group Performance Status 0-2
• 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)

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<1.0×10\^9/L Platelets<75×10\^9/L ALT or AST is 2.5 times higher than the upper limits of normal (ULN), serum bilirubin are 1.5 times higher than the ULN.

eGFR is lower than 30ml/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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital — Shanghai

Identifiers

NCT: NCT07514169 · SILVERGLO

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗