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
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
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.
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.
Shanghai Institute of Hematology, Rui-Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, China
RECRUITING2-year PFS rate
Time frame: up to approximately 2 years
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.
Time frame: Baseline up to data cut-off (up to approximately 2 years)
2-year OS rate
2-year OS rate
Time frame: 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.
Time frame: 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.
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
Percentage of participants with complete or partial response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
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
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.
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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)
Quality of Life will be assessed by EORTC QLQ-C30 (Verison 3.0).
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)
Quality of Life will be assessed by EORTC QLQ-ELD14.
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)
Quality of Life will be assessed by FACT-Lym LymS.
Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion