NCT03206918CompletedPhase 2
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)
BeiGene11 sites in 1 country91 target enrollmentStarted: March 9, 2017Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 91
- Locations
- 11
- Primary Endpoint
- Overall Response Rate (ORR) by Independent Review Committee (IRC)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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)
Exclusion Criteria
- •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
- •History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Zanubrutinib
Experimental
Intervention: Zanubrutinib (Drug)
Outcomes
Primary Outcomes
Overall Response Rate (ORR) by Independent Review Committee (IRC)
Time Frame: Up to 1 year and 4 months
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.
Secondary Outcomes
- Progression-free Survival (PFS): Percentage of Participants Progression/Death Event Free(6, 12, 24, and 36 months)
- 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)
- 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)
Investigators
Study Sites (11)
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