Subjects with Waldenström’s Macroglobulinemia (WM) who require therapy according to the consensus panel criteria from the 7th International Workshop on Waldenström’s Macroglobulinemia MedDRA version: 21.0 Level: PT Classification code 10047801 Term: Waldenstrom's macroglobulinaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: zanubrutinib (BGB-3111)
Product Code: BGB-3111
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not yet established
CAS Number: 1691249-45-2
Current Sponsor code: BGB-3111
Other d
Sponsors
BeiGene Ltd. c/o BeiGene USA Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Clinical and definitive histologic diagnosis of WM. Subjects must either have relapsed/refractory disease OR be treatment naïve and considered by their treating physician to be unsuitable for standard chemoimmunotherapy regimens. a. For subjects who have received no prior therapy for WM: "Unsuitable" for treatment with a standard chemoimmunotherapy regimen must be a physician-determined status based on co-morbidities and risk factors. Physicians will need to provide and document organ system(s) and specific reason(s) for subject being considered unsuitable. Patient preference does not meet the eligibility requirement for a treatmentnaïve subject to be unsuitable for treatment with a standard chemoimmunotherapy regimen. 2. Meeting at least one criterion for treatment according to consensus panel criteria from the Seventh IWWM (Dimopoulos et al 2014) 3. Measurable disease, as defined by serum IgM level >0.5 g/dL 4. Age = 18 years old 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 6. Adequate bone marrow function defined as: - Neutrophils = 0.75 x 10 power 9/L independent of growth factor support within 7 days of study entry - Platelets = 50 x 10 power 9/L, independent of growth factor support or transfusion within 7 days of study entry 7. 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]) based on ideal body mass. 11. Subjects who relapse after autologous stem cell transplant are eligible if they are at least 3 months after transplant, and are eligible after allogeneic transplant if they are at least 6 months posttransplant. To be eligible after either type of transplant, subjects should have no active infections or in the case of allogeneic transplant relapse, no active acute graft versus host disease (GvHD) of any grade, and no chronic GvHD other than mild skin, oral, or ocular GvHD not requiring systemic immunosuppression. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 145
Exclusion criteria
Exclusion criteria: 1. Prior exposure to a BTK inhibitor. 2. Evidence of disease transformation at the time of study entry. 3. Corticosteroids given with antineoplastic intent within 7 days, or chemotherapy, targeted therapy, or radiation therapy within 3 weeks, or antibody-based therapy within 4 weeks of the start of study drug. 4. Major surgery within 4 weeks of study treatment. 5. Ongoing toxicity of = Grade 2 from prior anticancer therapy (except for alopecia, absolute neutrophil count [ANC] and platelets). For ANC and platelets, please follow inclusion criteria #6 [neutrophils] 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 such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease (congestive heart failure) as defined by the New York Heart Association (NYHA) Functional Classification, or history of myocardial infarction within 6 months of screening. 8. QTcF prolongation (defined as a QTcF > 480 msec) 9. Active, clinically significant Electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block Type II, or third degree AV block. 10. 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. 11. Uncontrolled active systemic infection or recent infection requiring parenteral anti-microbial therapy that was completed =14 days before the first dose of study drug. 12. Known infection with human immunodeficiency virus (HIV), or serologic status reflecting active hepatitis B or hepatitis C as follows: a) Presence of hepatitis B surface antigen [HBsAg] or anti-hepatitis core antibody (anti-HBc). Patients with presence of anti-HBc, but absence of HBsAg are eligible if hepatitis B virus (HBV) DNA is undectectable and if they are willing to undergo monthly monitoring for HBV reactivation. b) Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are elegible if HCV ribonucleic acid (RNA) is undetectable.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of zanubrutinib (BGB-3111) vs ibrutinib in subjects with MYD88MUT WM;Secondary Objective: To further compare the efficacy, clinical benefit, and anti-lymphoma effects of zanubrutinib (BGB-3111) vs ibrutinib in subjects with MYD88MUT WM. To evaluate safety and tolerability of zanubrutinib (BGB-3111) versus ibrutinib in subjects with MYD88MUT WM, as measured by the incidence and severity of adverse events;Primary end point(s): The primary endpoint is the proportion of subjects in Cohort 1 achieving either CR or VGPR, as determined by independent review committee (IRC) using an adaptation of the response criteria updated at the Sixth IWWM (Owen et al. 2013 and NCCN Guidelines, Lymphoplasmacytic Lymphoma/Waldenström’s Macroglobulinemia 2015: v2).;Timepoint(s) of evaluation of this end point: As determined by independent review committee (IRC). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Major response rate (MRR) as assessed by the IRC, defined as the proportion of subjects achieving CR, VGPR, or partial response (PR) - Duration of response (DOR) as assessed by the IRC, defined as the time from first determination of response (CR, VGPR or PR) (per modified IWWM criteria) until first documentation of progression (per modified IWWM criteria) or death, whichever comes first - Rate of CR or VGPR as assessed by the Investigator - DOR as assessed by the Investigator, defined as the time from first determination of response (CR, VGPR or of PR) (per modified IWWM criteria) until first documentation of progression (per modified IWWM criteria) or death, whichever comes first - Progression-free survival (PFS) as assessed by the IRC, defined as time from randomization to the first documentation of progression (per modified IWWM criteria) or death, whichever occurs first - PFS as assessed by the Investigator, defined as time from randomization to the first documentation of progression (per modified IWWM criteria) or death, whichever occurs first - Resolution of treatment-precipitating symptoms, defined as the absence of the symptoms that triggered initiation of study treatment (per the IWWM treatment guidelines) at any point during study treatment - Anti-lymphoma effect, defined as any reduction in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or hepatosplenomegaly by CT scan, at any time during the course of study treatment;Timepoint(s) of evaluation of this end point: Major response rate (MRR): As assessed by the Independent Review Committee (IRC). Duration of Response (DOR): As assessed by the investigator or the IRC. Rate of CR or VGPR: Complete Response (CR): every 24 weeks, at time of suspected complete response (CR), and as clinically indicated. Very good partial response (VGPR): as assessed by the investigator. Progression Free Survival: As assessed b | — |
Countries
Australia, Belgium, Czech Republic, France, Germany, Greece, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactBeiGene Clinical Support
BeiGene USA, Inc.
Outcome results
None listed