A Phase 3, Randomized, Open-Label, Multicenter Study Comparing the Efficacy and Safety of the medications BGB-3111 and Ibrutinib in Subjects with Waldenström’s Macroglobulinemia (WM)
- Conditions
- Subjects with Waldenström’s Macroglobulinemia (WM) who require therapy according to the consensus panel criteria from the 7th International Workshop on Waldenström’s MacroglobulinemiaMedDRA version: 21.0Level: PTClassification code 10047801Term: Waldenstrom's macroglobulinaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002980-33-GB
- Lead Sponsor
- BeiGene Ltd. c/o BeiGene USA Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 210
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 CockcroftGault 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 post-transplant. 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
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 undetectable and if
they are willing to undergo monthly monitoring for HBV reactivationb).
b) Presence of hepatitis C virus (HCV] antibody. Patients with presence of HCV antibody are eligible if HCV ribonucleic acid (RNA) is undetectable.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.<br><br>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<br>Lymphoma/Waldenström’s Macroglobulinemia 2015: v2).;Timepoint(s) of evaluation of this end point: As determined by independent review committee (IRC).
- Secondary Outcome Measures
Name Time Method