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

Official title

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

Overview

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

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.

Interventions

• 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
• 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

Primary outcome measures

• 2-year PFS rate [Time frame: up to approximately 2 years]

Secondary outcome measures (9)

• Progression free survival [Time frame: Baseline up to data cut-off (up to approximately 2 years)]
• 2-year OS rate [Time frame: Baseline up to data cut-off (up to approximately 2 years)]
• Overall survival [Time frame: Baseline up to data cut-off (up to approximately 2 years)]
• Complete response rate [Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]]
• Overall response rate [Time frame: 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 [Time frame: From enrollment to study completion, a maximum of 5 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) [Time frame: 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) [Time frame: 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) [Time frame: Day 1 of Cycles 1 and 4 (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 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

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Institute of Hematology, Rui-Jin Hospital affiliated to Shanghai Jiao Tong Univer — Shanghai

Identifiers

NCT: NCT06522555 · POTENT STUDY

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗