Efficacy and Safety of Zanubrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

NCT03206918 | Completed Phase 2 Results DMC

• 2 other identifiers: BGB-3111-205CTR20160890
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 11

Brief Summary

This was a single-arm, open-label, multi-center Phase 2 study in participants with histologically documented CLL/SLL who have relapsed after or refractory to ≥ 1 prior treatment regimen(s). The study is composed of an initial screening phase, a single-arm treatment phase, and a follow-up phase.

Conditions

Relapsed or Refractory Chronic Lymphocytic Leukemia; Relapsed or Refractory Small Lymphocytic Lymphoma

Keywords

Bruton's tyrosine kinase; Chronic lymphocytic leukemia; Relapsed/refractory; Zanubrutinib

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) by Independent Review Committee (IRC)

  ORR is defined as the number of participants who achieve a best response of CR or, CRi, Nodular Partial Response, PR, and PR with Lymphocytosis as assessed by IRC per the modified IWCLL Guidelines in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with SLL.

  Up to 1 year and 4 months

Secondary Outcomes (5)

• Progression-free Survival (PFS): Percentage of Participants Progression/Death Event Free

  6, 12, 24, and 36 months

• Duration of Response (DOR): Event Free Rate - Percentage of Participants Who Remained Event Free

  6, 12, 24, and 36 months

• Time to Response (TTR)

  Up to 3.5 years

• Overall Response Rate as Determined by the Investigator

  up to 3.5 years

• Number of Participants Experiencing Adverse Events (AEs)

  Up to 3.5 years

Study Arms (1)

Zanubrutinib

EXPERIMENTAL

Drug: Zanubrutinib

Interventions

Zanubrutinib DRUG

Zanubrutinib 160 mg (two - 80 mg white opaque capsules) taken by mouth (PO) twice a day (BID)

Also known as: BGB-3111

Zanubrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis with at least one criterion for treatment according to International workshop on chronic lymphocytic leukemia (IWCLL)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Measurable disease by contrast enhanced computerized tomography / magnetic resonance imaging (CT/MRI).
• Previously treated with a minimum of 1 prior line of standard chemotherapy-containing regimen (with completion of ≥2 treatment cycles).
• Documented failure to achieve at least partial response (PR) or documented disease progression after response to the most recent treatment regimen. Refractory disease is defined as treatment failure (stable disease, non-response, progressive disease \[PD\]) or disease progression within 6 months after the most recent prior therapy (Hallek et al, 2008).
• Neutrophils ≥ 0.75 x 109/L independent of growth factor support within 7 days of study entry
• Platelets ≥ 50 x 109/L, independent of growth factor support or transfusion within 7 days of study entry
• Creatinine clearance of ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate \[eGFR\] from the Modification of Diet in Renal Disease \[MDRD\])
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN
• Bilirubin ≤2 x ULN (unless documented Gilbert's syndrome)
• International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5 x ULN.
• Participants may be enrolled who relapse after autologous stem cell transplant if they are at least 6 months after transplant.
• Life expectancy of \>4 months
• Echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥50%; (AHA, 2016)

You may not qualify if:

• Current or history of central nervous system (CNS) lymphoma
• Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor
• Prior corticosteroids given in excess of prednisone 10 mg/day or its equivalent with antineoplastic intent within 7 days.
• Major surgery within 4 weeks of screening
• Not recovered from toxicity of any prior anti-cancer therapy to \<Grade 1 (except for alopecia, absolute neutrophil count (ANC) and platelets.
• History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent
• Currently active clinically significant cardiovascular disease
• QTcF \>480 msecs based on Fridericia's formula or other significant electrocardiogram abnormalities including second degree atrioventricular (AV) block Type II, or third degree AV block
• Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
• Active infection including infections requiring oral or intravenous anti-microbials
• Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction \[PCR\]).
• Has received allogenic hematopoietic stem cell transplantation prior to enrollment
• Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the participants's safety, or put the study at risk
• Requires ongoing treatment with any medication which is a strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitor or strong CYP3A inducer
• Known or clinically suspected Richter's transformation at the time of study entry

Sponsors & Collaborators

• BeiGene: lead

Study Sites (11)

Peking University Peoples Hospital

Beijing, Beijing Municipality, 100044, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

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

Wuhan, Hubei, 430030, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Institute of Hematology and Hospital of Blood Disease

Tianjin, Tianjin Municipality, 300020, China

Location

Related Publications (4)

• Xu W, Yang S, Zhou K, Pan L, Li Z, Zhou J, Gao S, Zhou D, Hu J, Feng R, Huang H, Ji M, Guo H, Huang J, Novotny W, Feng S, Li J. Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with the BTK inhibitor zanubrutinib: phase 2, single-arm, multicenter study. J Hematol Oncol. 2020 May 11;13(1):48. doi: 10.1186/s13045-020-00884-4.

  PMID: 32393328 RESULT

• Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.

  PMID: 38502198 DERIVED

• Xu W, Yang S, Zhou K, Pan L, Li Z, Gao S, Zhou D, Hu J, Feng R, Huang H, Wang T, Li D, Ji M, Guo H, Zhao X, Wu B, Yu Y, Wang Y, Huang J, Novotny W, Li J. Zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: final results and correlative analysis of lymphocytosis. Leuk Lymphoma. 2023 Mar;64(3):712-716. doi: 10.1080/10428194.2022.2164692. Epub 2023 Feb 17. No abstract available.

  PMID: 36799536 DERIVED

• Xu W, Yang S, Tam CS, Seymour JF, Zhou K, Opat S, Qiu L, Sun M, Wang T, Trotman J, Pan L, Gao S, Zhou J, Zhou D, Zhu J, Song Y, Hu J, Feng R, Huang H, Su D, Shi M, Li J. Zanubrutinib Monotherapy for Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Adv Ther. 2022 Sep;39(9):4250-4265. doi: 10.1007/s12325-022-02238-7. Epub 2022 Jul 28.

  PMID: 35900694 DERIVED

MeSH Terms

Conditions

Recurrence; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2017
• First Posted: July 2, 2017
• Study Start: March 9, 2017
• Primary Completion: June 15, 2018
• Study Completion: September 10, 2020
• Last Updated: October 26, 2024
• Results First Posted: September 25, 2020

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (11)