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Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Phase 1
Completed
Conditions
Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Interventions
Registration Number
NCT04436107
Lead Sponsor
BeiGene
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 and tolerability of zanubrutinib in combination with lenalidomide in participants with R/R DLBCL by dose escalating lenalidomide

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
66
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part 2 : Zanubrutinib+LenalidomideZanubrutinibZanubrutinib for up to 48 months Lenalidomide at the RP2D dose determined from Part 1 administered on Days 1 - 21 of each 28-Day cycle for up to 48 months
Part 1 : Zanubrutinib + LenalidomideZanubrutinibZanubrutinib for up to 48 months Lenalidomide on Days 1 - 21 of each 28-Day cycle for up to 48 months
Part 1 : Zanubrutinib + LenalidomideLenalidomideZanubrutinib for up to 48 months Lenalidomide on Days 1 - 21 of each 28-Day cycle for up to 48 months
Part 2 : Zanubrutinib+LenalidomideLenalidomideZanubrutinib for up to 48 months Lenalidomide at the RP2D dose determined from Part 1 administered on Days 1 - 21 of each 28-Day cycle for up to 48 months
Primary Outcome Measures
NameTimeMethod
Part 1: Number of Participants Experiencing Severe Adverse Events (SAEs)Up to 48 months
Part 1: Number of Participants Experiencing Adverse Events (AEs)Up to 48 months
Part 2: Overall Response Rate (ORR)Up to 48 months

The proportion of participants who achieve either a partial response (PR) or complete response (CR)

Secondary Outcome Measures
NameTimeMethod
Time to Response (TTR)Up to 48 months
Part 1: Overall Response Rate (ORR)Up to 48 months

The proportion of participants who achieve either a partial response (PR) or complete response (CR)

Maximum Concentration (Cmax)C1D1 and C1D21 up to 8 hours post-dose
Progression-Free Survival (PFS)Up to 48 months
Time to reach maximum plasma concentration (Tmax)C1D1 and C1D21 up to 8 hours post-dose
Apparent Clearance (CL/F)C1D1 and C1D21 up to 8 hours post-dose
Complete Response Rate (CRR)Up to 48 months
Duration of Response (DOR)Up to 48 months
Area Under the Curve from Zero to Last Measurable Concentration (AUC0-t)Cycle 1 Day 1 (C1D1) and C1D21 up to 8 hours post-dose
Receptor Occupancy (Ro)C1D1 and C1D21 up to 8 hours post-dose

Trial Locations

Locations (10)

Beijing Friendship Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

Sun Yat Sen University Cancer Center

🇨🇳

Guangzhou, Guangdong, China

Henan Cancer Hospital

🇨🇳

Zhengzhou, Henan, China

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

🇨🇳

Wuhan, Hubei, China

Jilin Cancer Hospital

🇨🇳

Changchun, Jilin, China

Fudan University Shanghai Cancer Center

🇨🇳

Shanghai, Shanghai, China

Shanghai East Hospital

🇨🇳

Shanghai, Shanghai, China

West China Hospital, Sichuan University

🇨🇳

Chengdu, Sichuan, China

Tianjin Medical University Cancer Institute and Hospital

🇨🇳

Tianjin, Tianjin, China

Zhejiang Cancer Hospital

🇨🇳

Hangzhou, Zhejiang, China

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