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

Relapsed/Refractory Diffuse Large B-Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04436107
• Other study ID #: BGB-3111-110
• Status: Completed
• Phase: Phase 1
• Start date: September 11, 2020
• Est. completion date: March 28, 2024

Study information

• Verified date: April 2024
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: March 28, 2024
• Est. primary completion date: March 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Intervention

Drug:
• Zanubrutinib
160 mg administered orally twice daily (BID)
• Lenalidomide
Administered as specified in the treatment arm

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	West China Hospital · Sichuan University	Chengdu	Sichuan
China	Sun Yat-sen University Cancer Center	Guangzhou
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Fudan University Shanghai Cancer Center	Shanghai
China	Shanghai East Hospital	Shanghai
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants Experiencing Adverse Events (AEs)		Up to 48 months
Primary	Part 1: Number of Participants Experiencing Severe Adverse Events (SAEs)		Up to 48 months
Primary	Part 2: Overall Response Rate (ORR)	The proportion of participants who achieve either a partial response (PR) or complete response (CR)	Up to 48 months
Secondary	Part 1: Overall Response Rate (ORR)	The proportion of participants who achieve either a partial response (PR) or complete response (CR)	Up to 48 months
Secondary	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
Secondary	Maximum Concentration (Cmax)		C1D1 and C1D21 up to 8 hours post-dose
Secondary	Time to reach maximum plasma concentration (Tmax)		C1D1 and C1D21 up to 8 hours post-dose
Secondary	Apparent Clearance (CL/F)		C1D1 and C1D21 up to 8 hours post-dose
Secondary	Receptor Occupancy (Ro)		C1D1 and C1D21 up to 8 hours post-dose
Secondary	Complete Response Rate (CRR)		Up to 48 months
Secondary	Time to Response (TTR)		Up to 48 months
Secondary	Progression-Free Survival (PFS)		Up to 48 months
Secondary	Duration of Response (DOR)		Up to 48 months