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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03206918
Recruitment Status : Completed
First Posted : July 2, 2017
Results First Posted : September 25, 2020
Last Update Posted : March 25, 2021
Information provided by (Responsible Party):

Brief Summary:
This is 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.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Chronic Lymphocytic Leukemia Relapsed or Refractory Small Lymphocytic Lymphoma Drug: Zanubrutinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 91 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate Safety and Efficacy of BGB-3111, a Bruton's Tyrosine Kinase (BTK) Inhibitor in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Actual Study Start Date : March 9, 2017
Actual Primary Completion Date : June 15, 2018
Actual Study Completion Date : September 1, 2020

Arm Intervention/treatment
Experimental: Zanubrutinib Drug: Zanubrutinib
Zanubrutinib 160 mg (two - 80 mg white opaque capsules) taken by mouth (PO) twice a day (BID)
Other Name: BGB-3111

Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 12 months ]
    ORR is defined as the number of participants who achieve a best response of Complete Response (CR) or, Complete Response with Incomplete Bone Marrow Recovery (CRi), Nodular Partial Response, Partial Response (PR), and PR with Lymphocytosis as assessed by IRC per the modified IWCLL Guidelines in patients with CLL and the Revised Criteria for Response for Malignant Lymphoma in patients with SLL.

Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Up to 3 years ]
    From the first dose of zanubrutinib to the date of PD or death, whichever occurs first

  2. Duration of Response (DOR) [ Time Frame: Up to 3 years ]
    From the date that response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first

  3. Time to Response (TTR) [ Time Frame: Up to 3 years ]
    From the date of the first dose of zanubrutinib to the time the response criteria are first met

  4. Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 3 years ]
  5. Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 3 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  1. Confirmed diagnosis with at least one criterion for treatment according to IWCLL
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

3.Measurable disease by contrast enhanced computerized tomography / magnetic resonance imaging (CT/MRI).

4. Previously treated with a minimum of 1 prior line of standard chemotherapy-containing regimen (with completion of ≥2 treatment cycles).

5. 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).

6. Neutrophils ≥ 0.75 x 109/L independent of growth factor support within 7 days of study entry

7. Platelets ≥ 50 x 109/L, independent of growth factor support or transfusion within 7 days of study entry

8. 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])

9. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN

10. Bilirubin ≤2 x ULN (unless documented Gilbert's syndrome)

11. International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5 x ULN.

12. Participants may be enrolled who relapse after autologous stem cell transplant if they are at least 6 months after transplant.

13. Life expectancy of >4 months 14. Echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥50%; (AHA, 2016)

Key Exclusion Criteria:

  1. Current or history of central nervous system (CNS) lymphoma
  2. Prior exposure to a BTK inhibitor
  3. Prior corticosteroids given in excess of prednisone 10 mg/day or its equivalent with antineoplastic intent within 7 days.
  4. Major surgery within 4 weeks of screening
  5. Not recovered from toxicity of any prior anti-cancer therapy to <Grade 1 (except for alopecia, absolute neutrophil count (ANC) and platelets.
  6. 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
  7. Currently active clinically significant cardiovascular disease
  8. 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
  9. 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
  10. Active infection including infections requiring oral or intravenous anti-microbials
  11. Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction [PCR]).
  12. Has received allogenic hematopoietic stem cell transplantation prior to enrollment
  13. 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
  14. Requires ongoing treatment with any medication which is a strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitor or strong CYP3A inducer
  15. Known or clinically suspected Richter's transformation at the time of study entry
  16. History of stroke or intracranial hemorrhage within 6 months prior to enrollment

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03206918

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China, Beijing
Peking University People's Hospital
Beijing, Beijing, China, 100082
Peking Union Medical College Hospital
Beijing, Beijing, China, 100730
China, Fujian
Fujian Medical University Union Hospital
Fuzhou, Fujian, China, 350001
China, Guangzhou
Nanfang Hospital
Guangdong, Guangzhou, China, 510515
China, Henan
Henan Cancer Hospital
Zhengzhou, Henan, China, 450008
China, Hubei
Tongji Hospital of Tongji Medical College of HUST
Wuhan, Hubei, China, 430030
China, Jiangsu
Jiangsu Province Hospital
Nanjing, Jiangsu, China, 210029
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China, 215006
China, Jinlin
The First Affilliated Hospital of Jinlin University
Changchun, Jinlin, China, 130021
China, Sichuan
West China Hospital of Sichuan University
Chengdu, Sichuan, China, 610041
China, Tianjin
Tianjin Hematonosis Hospital
Tianjin, Tianjin, China, 300020
Sponsors and Collaborators
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Principal Investigator: Jianyong Li, PhD The First Affiliated Hospital with Nanjing Medical University
  Study Documents (Full-Text)

Documents provided by BeiGene:
Statistical Analysis Plan  [PDF] March 16, 2018
Study Protocol  [PDF] October 25, 2017

Publications of Results:
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Responsible Party: BeiGene Identifier: NCT03206918    
Other Study ID Numbers: BGB-3111-205
CTR20160890 ( Registry Identifier: Center for drug evaluation, CFDA )
First Posted: July 2, 2017    Key Record Dates
Results First Posted: September 25, 2020
Last Update Posted: March 25, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BeiGene:
Bruton's tyrosine kinase
Chronic lymphocytic leukemia
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action