Clinical trial NCT04436107: Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Official title: A Phase 1, Open Label, Multiple Dose, Dose Escalation and Expansion Study of Bruton Tyrosine Kinase (BTK) Inhibitor, Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2020-06-17
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the maximum tolerated doses (MTD) and the recommended Phase 2 dose (RP2D), and safety, tolerability, and efficacy of zanubrutinib in combination with lenalidomide in participants with R/R DLBCL


Eligibility criteria: Key Inclusion Criteria:

1. Histologically confirmed DLBCL, all participants must provide sufficient archival or fresh tumor tissue samples for evaluation by immunohistochemistry (IHC) and Gene Expression Profiling (GEP).
2. Relapsed or refractory disease, defined as either: 1) progression of disease after having achieved disease remission (complete response \[CR\] or partial response \[PR\]) , or 2) stable disease (SD), or progressive disease (PD) at completion of the treatment regimen preceding entry to the study.
3. Participants who have not received high dose therapy/stem cell transplantation (HDT/SCT) must be ineligible for HDT/SCT.
4. Measurable disease as defined by at least 1 lymph node \>1.5 cm in longest diameter, or at least 1 extra-nodal lesion \>1.0 cm in longest diameter, and measurable in 2 perpendicular dimensions.
5. Received an appropriate first-line therapy for DLBCL,defined as an anti CD20 antibody and an appropriate anthracycline-based combination therapy for at least 2 cycles, unless the patient is intolerant or had disease progression before Cycle 2..

Key Exclusion Criteria:

1. Current or history of central nervous system (CNS) lymphoma.
2. Histologically transformed lymphoma.
3. History of allogeneic stem-cell transplantation.
4. Prior exposure to a BTK inhibitor.
5. Prior exposure to lenalidomide or thalidomide.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug to 30 days after last dose. Maximum time on treatment in Part 1 was 1260 days.
measure: Part 2: Overall Response Rate (ORR)
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
Secondary outcomes:
measure: Part 1: Overall Response Rate (ORR)
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up in Part 1 was 42 months.
measure: Area Under the Plasma Concentration-time Curve From Zero to 8 Hours Postdose (AUCt) of Zanubrutinib After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Zanubrutinib After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Zanubrutinib After a Single Dose
timeFrame: Cycle 1 Day 1, 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Maximum Plasma Concentration (Cmax) of Zanubrutinib After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Time to Maximum Plasma Concentration (Tmax) of Zanubrutinib After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Time to the Last Quantifiable Concentration (Tlast) of Zanubrutinib After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Apparent Terminal Elimination Half-life (T1/2) of Zanubrutinib After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Apparent Volume (CL/F) of Zanubrutinib After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Apparent Clearance (Vz/F) of Zanubrutinib After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Accumulation Ratio of AUCt for Zanubrutinib
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Accumulation Ratio of Cmax for Zanubrutinib
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Area Under the Plasma Concentration-time Curve From Zero to 8 Hours Postdose (AUCt) of Lenalidomide After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: AUClast of Lenalidomide After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: AUCinf of Lenalidomide After a Single Dose
timeFrame: Cycle 1 Day 1 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Cmax of Lenalidomide After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Tmax of Lenalidomide After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Tlast of Lenalidomide After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: T1/2 of Lenalidomide After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: CL/F of Lenalidomide After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Vz/F of Lenalidomide After a Single Dose and at Steady State
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Accumulation Ratio of AUCt for Lenalidomide
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Accumulation Ratio of Cmax for Lenalidomide
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 21 at predose and 0.5, 1, 2, 3, 4, and 8 hours postdose
measure: Part 1: Overall Response Rate by Immunohistochemistry Subtypes
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up in Part 1 was 42 months.
measure: Part 1: Overall Response Rate by Gene Expression Profiling (GEP) Subtypes
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up in Part 1 was 42 months.
measure: Part 2: Overall Response Rate by Immunohistochemistry Subtypes
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Overall Response Rate by Gene Expression Profiling Subtypes
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Complete Response Rate (CRR)
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
measure: Part 2: Complete Response Rate by Immunohistochemistry Subtypes
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Complete Response Rate by Gene Expression Profiling Subtypes
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Duration of Response (DOR)
timeFrame: From first dose to the end of study; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
measure: Part 2: Duration of Response by Immunohistochemistry Subtypes
timeFrame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Duration of Response by Gene Expression Profiling Subtypes
timeFrame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Progression-free Survival (PFS)
timeFrame: From first dose to the end of study; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
measure: Part 2: Progression-Free Survival by Immunohistochemistry Subtypes
timeFrame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Progression-Free Survival by Gene Expression Profiling Subtypes
timeFrame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Time to Response (TTR)
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 24 months in Part 2 and 31 months in the RP2D group.
measure: Part 2: Time to Response by Immunohistochemistry Subtypes
timeFrame: Response was assessed every 12 weeks for the first 48 weeks and every 16 weeks for the next 48 weeks and every 24 weeks thereafter; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Time to Response by Gene Expression Profiling Subtypes
timeFrame: From first dose to the end of study; maximum time on follow-up was 31 months in the RP2D group.
measure: Part 2: Number of Participants With Treatment-emergent Adverse Events
timeFrame: From first dose of study drug to 30 days after last dose. Maximum time on treatment in Part 2 was 701 days.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: