Zanubrutinib Monotherapy in Relapsed/Refractory Central Nervous System Lymphoma

CNS Lymphoma Clinical Trial

Official title:

Zanubrutinib Monotherapy in Relapsed/Refractory Central Nervous System Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05117814
• Other study ID #: BGB-3111-2001-IIT
• Status: Recruiting
• Phase: N/A
• Start date: September 2021
• Est. completion date: July 2025

Study information

• Verified date: August 2022
• Source: Peking University People's Hospital
• Contact: Shenmiao Yang, MD
• Phone: 134399999810
• Email: yangshenmiao[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Zanubrutinib is a novel BTK inhibitor with proven activity in patients with various B-cell lymphomas addicted to the B-cell receptor signaling pathway.

Description:

Studies involving gene expression profiling and next generation sequencing have demonstrated that CNS lymphomas mostly are of the ABC-subtype and harbor mutations that reinforce BCR signaling. Ibrutinib, as the first BTK inhibitor, showed substantial activity in patients with R/R PCNSL and R/R SCNSL. Zanubrutinib is a novel BTK inhibitor with proven activity in patients with various B-cell lymphomas addicted to the B-cell receptor signaling pathway. In addition, pharmacological studies demonstrated the free drug exposure of zanubrutinib at 160 mg BID is roughly 10 times that of ibrutinib at 560 mg QD, and penetration into the CNS by zanubrutinib and ibrutinib is similar, suggesting the potential activity of zanubrutinib in the treatment of CNS lymphomas. However, the outcome of R/R PCNSL and R/R SCNSL patients treated with zanubrutinib monotherapy is still unclear.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 2025
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Key inclusion criteria:

1. Able to understand and willing to sign a written informed consent document

2. Men and woman at least 18 years of age on the day of consenting to the study

3. Histologically documented DLBCL.

4. Relapsed/refractory PCNSL or relapsed/refractory SCNSL

5. Patients with parenchymal lesions must have unequivocal evidence of disease progression on imaging (MRI or the brain or head CT) prior to study enrollment. For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells and/or imaging findings consistent with CSF disease prior to study enrollment.

6. An ECOG performance status=2

7. Adequate bone marrow and organ function shown by:

(1) Neutrophils = 0.75 x 109/L independent of growth factor support within 7 days of study entry (2) Platelets = 50 x 109/L independent of growth factor support or transfusion within 7 days of study entry (3) Creatinine clearance of = 30 mL/min (4) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 x upper limit of normal (ULN) (5) Bilirubin = 1.5 x ULN (6) International normalized ratio = 1.5 and activated partial thromboplastin time = 1.5 x ULN.

8. Recovered to grade 1 toxicity from prior therapy before the first dose of study drug 9. Agree to use highly effective methods of birth control during the period of therapy and for 3 months after the last dose of the study drug.

Exclusion Criteria:

1. Patients with SCNSL actively receiving treatment for extra-CNS disease

2. Concurrently using other approved or investigational antineoplastic agents

3. Prior chemotherapy, targeted therapy, or radiation therapy within 4 weeks

4. Prior exposure to a BTK inhibitor

5. Concurrently using more than 8mg of dexamethasone daily or the equivalent

6. History of other active malignancies within 2 years of study entry

7. Major surgery within 4 weeks of screening or not recovered from the side effects of such surgery

8. Known to have human immunodeficiency virus (HIV) infection

9. Known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests

10. Active infection systemic including infections requiring oral or intravenous antimicrobials

11. Currently active clinically significant cardiovascular disease

12. QTcF > 480 msecs or other significant electrocardiogram (ECG) abnormalities

13. Unable to swallow capsules or disease significantly affecting gastrointestinal function

14. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could have compromised the patient's safety, or put the study at risk

15. Required ongoing treatment with medication that are strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers

16. History of stroke or intracranial hemorrhage within 6 months prior to enrollment

17. Inability to comply with study procedures

18. Pregnant or lactating women

19. Prior allogenic hematopoietic stem cell transplantation (autologous stem cell transplant is NOT an exclusion)

Related Conditions & MeSH terms

• CNS Lymphoma
• Lymphoma

Intervention

Drug:
• Zanubrutinib
as long as 24 months or consolidated with ASCT or WBRT after achieving PR or CR

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival (OS)	The time from the first dose to death.	4 years
Other	ctDNA	ctDNA In CSF.	2 years
Primary	Overall response rate (ORR)	Based on the Investigator assessed CR and PR, with the enhanced CT scan, the cerebrospinal fluid (CSF) examination, and the ophthalmological examination.	2 years
Secondary	Time to response (TTR)	Time from the first dose of zanubrutinib to the first assessment of >=PR	2 years
Secondary	Duration of response (DOR)	Time from the first assessment of >=PR to symptom, CT scan, and/ or CSF confirmed progressive disease (PD)	2 years
Secondary	The concentration of zanunbrutinib in CSF and plasma	The concentration of zanunbrutinib in CSF and plasma 2 hours after taking the drug	2 months
Secondary	Progression-free survival (PFS)	The time from the first dose to PD or death whichever occurs earlier.	2 years
Secondary	Treatment-related adverse events (TRAE)	Adverse events during zanubrutinib treatment.	During zanubrutinib treatment until 30+/-7 days after discontinuation.