A Phase 3, Randomized Study of Zanubrutinib (BGB-3111) Compared with Ibrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Phase 3

Completed

• Conditions: Leukemia; blood cancer; 10024324

• Registration Number: NL-OMON56379
• Lead Sponsor: BeiGene, Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

1. Age 18 years or older
2. Confirmed diagnosis of CLL or SLL that meets the IWCLL criteria (Hallek et
al 2008)
3. CLL/SLL requiring treatment as defined by at least 1 of the following
criteria:
a. Evidence of progressive marrow failure as manifested by the development of,
or worsening of, anemia and/or thrombocytopenia
b. Massive (>= 6 cm below left costal margin), progressive, or symptomatic
splenomegaly
c. Massive nodes (>= 10 cm in longest diameter), or progressive or symptomatic
lymphadenopathy
d. Progressive lymphocytosis with an increase of > 50% over a 2-month period or
lymphocyte-doubling time of < 6 months. Lymphocyte-doubling time may be
obtained by linear regression extrapolation of absolute lymphocyte counts
obtained at intervals of 2 weeks over an observation period of 2 to 3 months.
In patients with initial blood lymphocyte counts of < 30 x 109/L (30,000/uL),
lymphocyte-doubling time should not be used as a single parameter to define
treatment indication. In addition, factors contributing to lymphocytosis or
lymphadenopathy other than CLL/SLL (eg, infection) should be excluded.
e. Constitutional symptoms, defined as any 1 or more of the following
disease-related symptoms or signs:
i. Unintentional weight loss of >= 10% within the previous 6 months
ii. Significant fatigue (ie, inability to work or perform usual activities)
iii. Fevers > 100.5ºF or 38ºC for >= 2 weeks without other evidence of infection
iv. Night sweats for > 1 month without evidence of infection
4. Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL. A
line of therapy is defined as completing at least 2 cycles of treatment of
standard regimen according to current NCCN or ESMO guidelines or of an
investigational regimen on a clinical trial
5. Measurable disease by CT/magnetic resonance imaging (MRI). Measurable
disease is defined as >= 1 lymph node > 1.5 cm in longest diameter and
measurable in 2 perpendicular diameters or an extranodal lesion must measure >
10 mm in longest perpendicular diameter (LPD).
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
7. Life expectancy >= 6 months
8. Adequate bone marrow function as defined by:
a. Absolute neutrophil count (ANC) >= 1000/mm3 (growth factor use is allowed),
except for patients with bone marrow involvement in which case ANC must be >=
750/mm3
- the screening hematology values confirming patient meets the ANC requirement
must be dated at least 14 days following the most recent administration of
pegfilgrastim and at least 7 days following the most recent administration of
other myeliod growth factions (eg, G-CSF, GM-CSF)
b. Platelet >= 75,000/mm3 (may be post-transfusion), except for patients with
bone marrow involvement by CLL in which case the platelet count must be >=
30,000/mm3
c. Hemoglobin >= 7.5 g/dL (may be post-transfusion)
9. Patient must have adequate organ function defined as:
a. Creatinine clearance >= 30 mL/min (as estimated by the Cockcroft-Gault
equation or the Modification of Diet in Renal Disease [MDRD] equation, or as
measured by nuclear medicine scan or 24-hour urine collection)
b. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase,
and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase <= 2.5 ×
upper limi

Exclusion Criteria

1. Known prolymphocytic leukemia or history of, or currently suspected,
Richter*s transformation (biopsy based on clinical suspicion may be needed to
rule out transformation)
2. Clinically significant cardiovascular disease including the following:
a) Myocardial infarction within 6 months before screening
b) Unstable angina within 3 months before screening
c) New York Heart Association class III or IV congestive heart failure
(Appendix 4)
d) History of clinically significant arrhythmias (eg, sustained ventricular
tachycardia, ventricular fibrillation, Torsades de Pointes)
e) QTcF > 480 milliseconds based on Fridericia*s formula
f) History of Mobitz II second-degree or third-degree heart block without a
permanent pacemaker in place
g) Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood
pressure measurements showing systolic blood pressure > 170 mmHg and diastolic
blood pressure > 105 mmHg at screening
3. Prior malignancy within the past 3 years, except for curatively treated
basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, or
carcinoma in situ of the cervix or breast
4. History of severe bleeding disorder such as hemophilia A, hemophilia B, von
Willebrand disease, or history of spontaneous bleeding requiring blood
transfusion or other medical intervention
5. History of stroke or intracranial hemorrhage within 180 days before first
dose of study drug
6. Severe or debilitating pulmonary disease
7. Unable to swallow study drug or disease significantly affecting
gastrointestinal function such as malabsorption syndrome, resection of the
stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory
bowel disease, or partial or complete bowel obstruction
8. Active fungal, bacterial, and/or viral infection requiring systemic therapy
9. Known central nervous system involvement by leukemia or lymphoma
10. Underlying medical conditions that, in the investigator*s opinion, will
render the administration of study drug hazardous or obscure the interpretation
of toxicity or AEs
11. Known infection with HIV or serologic status reflecting active viral
hepatitis B or C infection as follows:
a. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible
if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are
willing to undergo monitoring for HBV reactivation
b. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV
antibody are eligible if HCV RNA is undetectable
12. Moderate or severe hepatic impairment, ie, Child-Pugh class B or C
13. Major surgery within 4 weeks of the first dose of study drug
14. Prior treatment with a BTK inhibitor
15. Last dose of prior therapy for CLL/SLL <= 14 days before randomization, with
the following additional exclusion requirements:
a.Treatment with monoclonal antibody-based therapy within 28 days of first dose
of study drug
b. Treatment with chimeric antigen receptor T-cell therapy within 180 days of
first dose of study drug
c. Treatment with Chinese herbal medicine with anticancer intent within 28 days
of first dose of study drug
d. Chemotherapy or radiation treatment within 21 days of first dose of study
drug or hematopoietic s

Study & Design

• Study Type: Interventional
• Study Design: Not specified