Clinical trial NCT04116437: Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment
Official title: A Phase 2, Multicenter, Single-arm Study of Zanubrutinib (BGB-3111) in Patients With Previously Treated B-Cell Lymphoma Intolerant of Prior Treatment With Ibrutinib and/or Acalabrutinib
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Mantle Cell Lymphoma
Marginal Zone Lymphoma
Waldenstrom Macroglobulinemia
Keywords: BGB-3111
Zanubrutinib
Ibrutinib Intolerance
BTK Inhibitor
Acalabrutinib Intolerance
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2019-10-04
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety of zanubrutinib (also known as BGB-3111) in chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, mantle cell lymphoma, or marginal zone lymphoma patients who have become intolerant of prior ibrutinib and/or acalabrutinib treatment, by comparing intolerance to adverse event profile as assessed by the recurrence and the change in severity of adverse events.


Eligibility criteria: Key Inclusion Criteria:

1. Participants must meet protocol defined disease criteria requiring treatment for their respective disease prior to initiation of ibrutinib or acalabrutinib
2. Ibrutinib and acalabrutinib intolerance is defined as an unacceptable toxicity where, in the opinion of the investigator, treatment should be discontinued in spite of optimal supportive care as a result of one of the following:

   1. For ibrutinib and acalabrutinib intolerance events:

      * 1 or more ≥ Grade 2 nonhematologic toxicities for \>7 days (with or without treatment)
      * 1 or more ≥ Grade 3 nonhematologic toxicity of any duration
      * 1 or more Grade 3 neutropenia with infection or fever of any duration; or
      * Grade 4 heme toxicity which persists to the point that the investigator chose to stop therapy due to toxicity NOT progression.
   2. For acalabrutinib intolerance events only;

      * 1 or more ≥ Grade 1 nonhematologic toxicities of any duration with \> 3 recurrent episodes; or
      * 1 or more ≥ Grade 1 nonhematologic toxicities for \> 7 days (with or without treatment); or
      * Inability to use acid-reducing agents or anticoagulants (eg, proton pump inhibitors, warfarin) due to concurrent acalabrutinib use
3. Ibrutinib and/or acalabrutinib-related ≥ Grade 2 toxicities must have resolved to ≤ Grade 1 or baseline prior to initiating treatment with zanubrutinib. Grade 1 acalabrutinib-related toxicities must have resolved to Grade 0 or baseline prior to initiating treatment with zanubrutinib.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
5. Absolute neutrophil count (ANC) ≥ 1000/mm\^3 with or without growth factor support and platelet count ≥ 50,000/mm\^3 (may be post-transfusion), on or prior to C1D1 of zanubrutinib

Key Exclusion Criteria:

1. Clinically significant cardiovascular disease including the following:

   1. Myocardial infarction within 6 months before the Screening
   2. Unstable angina within 3 months before the Screening
   3. New York Heart Association class III or IV congestive heart failure
   4. History of sustained ventricular tachycardia, ventricular fibrillation, and/or Torsades de Pointes
   5. QT interval corrected by Fridericia's formula \> 480 milliseconds
   6. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
2. History of central nervous system (CNS) hemorrhage
3. Documented progressive disease (PD) during ibrutinib and/or acalabrutinib treatment.
4. Have received any anticancer therapy (other than immunotherapy) for CLL/SLL, WM, MCL, and MZL \< 7 days before any Screening assessments are performed or any immunotherapy treatment, taken alone or as part of a chemoimmunotherapy regimen, \< 4 weeks before any Screening assessments are performed
5. Requires ongoing need for corticosteroid treatment \> 10 mg daily of prednisone or equivalent corticosteroid. Note: Systemic corticosteroids must be fully tapered off/discontinued ≥ 5 days before the first dose of study drug is administered.

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

Primary outcomes:
measure: Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest.
timeFrame: 24 months
Secondary outcomes:
measure: Overall response as determined by investigator
timeFrame: 24 months
measure: Progression free survival (PFS) as determined by investigator
timeFrame: 24 months
measure: Patient reported outcomes as measured by EuroQol five dimension scale (EQ-5D)
timeFrame: 24 months
measure: Patient reported outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC)
timeFrame: 24 months
measure: Disease control rate as determined by investigator
timeFrame: 24 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers (Williams) Usor
state: Colorado
city: Newark
country: United States
facility: Christiana Care
state: Delaware
city: Fort Myers
country: United States
facility: Scri Florida Cancer Specialists South
state: Florida
city: Jacksonville
country: United States
facility: St Century Oncology
state: Florida
city: Saint Petersburg
country: United States
facility: Scri Florida Cancer Specialists North
state: Florida
city: Flossmoor
country: United States
facility: Healthcare Research Network Iii, Llc
state: Illinois
city: Burnsville
country: United States
facility: Minnesota Oncology Burnsville Clinic
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Westbury
country: United States
facility: Clinical Research Alliance, Inc
state: New York
city: Eugene
country: United States
facility: Oncology Associates of Oregon Willamette Valley Cancer Center
state: Oregon
city: Fountain Hill
country: United States
facility: St Lukes University Health Network
state: Pennsylvania
city: Horsham
country: United States
facility: Abington Hematology Oncology Associates
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology, Pllc Nashville
state: Tennessee
city: Amarillo
country: United States
facility: Texas Oncology Amarillo
state: Texas
city: Austin
country: United States
facility: Texas Oncology Tyler Longview
state: Texas
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: McAllen
country: United States
facility: Texas Oncology McAllen South Second Street
state: Texas
city: Fairfax
country: United States
facility: Us Oncology Virginia Cancer Specialists, Pc
state: Virginia
city: Virginia Beach
country: United States
facility: Virginia Oncology Associates Hampton
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Spokane
country: United States
facility: Medical Oncology Associates
state: Washington
city: Madison
country: United States
facility: Ssm Health Cancer Care Dean Medical Center
state: Wisconsin
Study officials:
References:
citation: Shadman M, Flinn IW, Levy MY, Porter RF, Burke JM, Zafar SF, Misleh J, Kingsley EC, Yimer HA, Freeman B, Rao SS, Chaudhry A, Tumula PK, Gandhi MD, Manda S, Chen DY, By K, Xu L, Liu Y, Crescenzo R, Idoine A, Zhang X, Cohen A, Huang J, Sharman JP. Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study. Lancet Haematol. 2023 Jan;10(1):e35-e45. doi: 10.1016/S2352-3026(22)00320-9. Epub 2022 Nov 16.