The purpose of this study is to evaluate the efficacy of ibrutinib based on overall response rate (ORR) (partial response \[PR\] or better) by investigator assessment per the modified Consensus Response Criteria from the Sixth International Workshop on Waldenstrom's Macroglobulinemia (IWWM) (NCCN 2019), in Chinese participants with relapsed or refractory waldenstrom's macroglobulinemia.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Ibrutinib will be administered orally, once daily, at a dose of 420 mg (140 mg\*3 capsules taken together at one time).
The First Hospital of Jilin University
Changchun, China
First affiliated Hospital of Zhejiang University
Hangzhou, China
Institute of Hematology and Blood Diseases Hospital
Tianjin, China
Wuhan Union Hospital
Wuhan, China
Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved partial response (PR) or better (VGPR) per the modified consensus response criteria from sixth International Workshop on Waldenstrom's Macroglobulinemia (IWWM) (National Comprehensive Cancer Network \[NCCN\], 2019). PR: greater than or equal to (\>=) 50 percent (%) reduction of serum immunoglobulin M (IgM) from baseline, with reduction in lymphadenopathy/splenomegaly if present at baseline. Very Good Partial Response (VGPR): \>=90% reduction of serum IgM from baseline or normal serum IgM values, with reduction in lymphadenopathy/splenomegaly if present at baseline.
Time frame: From start of the treatment (Day 1) up to 49.3 months
Clinical Response Rate (CRR)
CRR was defined as the percentage of participants who achieved minor response (MR) or better according to the modified sixth IWWM (NCCN 2019) criteria as assessed by the investigator. MR: \>=25% but less than (\<) 50% reduction of serum IgM from baseline.
Time frame: From start of the treatment (Day 1) up to 49.3 months
Very Good Partial Response (VGPR) or Better Response Rate
VGPR or better response rate was defined as the percentage of participants who achieved VGPR or better according to the modified sixth IWWM (NCCN 2019) criteria as assessed by the investigator. VGPR: \>=90% reduction of serum IgM from baseline or normal serum IgM values, with reduction in lymphadenopathy/splenomegaly if present at baseline.
Time frame: From start of the treatment (Day 1) up to 49.3 months
Duration of Response (DOR)
DOR: duration from date of initial documentation of response (PR/better) to date of first documented progressive disease(PD), death or date of censoring if applicable, for responders (PR/better), as assessed by investigator. VGPR/PR: \>=90% reduction or normal serum IgM values (for VGPR) and \>=50% (for PR) reduction of serum IgM, with reduction in lymphadenopathy/splenomegaly if present at baseline. PD(at least 1): \>=25% IgM increase in serum IgM with \>=500 milligrams per deciliters(mg/dL) increase from nadir(lowest serum IgM value at any time from baseline), confirmation needed if IgM was sole PD criterion; new lymph nodes \>1.5 centimeters(cm), \>=50% increase in nadir in sum of product of diameters; 50% increase in longest diameter of previously identified node \>1cm in short axis; new splenomegaly; new extranodal disease; new/recurrent bone marrow involvement; new symptomatic disease(pleural effusion/Bing Neel syndrome/amyloidosis/light chain deposition/paraprotein mediated disorder).
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The Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an, China
Henan Cancer Hospital
Zhengzhou, China
Time frame: From the date of first documented response up to date of first documented PD or death (Day 1 up to 49.3 months)
Time to Response (TTR)
TTR was defined as the time from the date of first dose to the date of initial documentation of a response (PR or better) for responders. PR: \>=50% reduction of serum IgM from baseline, with reduction in lymphadenopathy/splenomegaly if present at baseline. VGPR: \>=90% reduction of serum IgM from baseline or normal serum IgM values, with reduction in lymphadenopathy/splenomegaly if present at baseline.
Time frame: From start of the treatment up to first documentation of PR or better (Day 1 up to 49.3 months)
Progression Free Survival (PFS)
PFS was defined as duration from the date of first dose to the date of disease progression or death, whichever occurs first, assessed according to the modified sixth IWWM (NCCN 2019) criteria. PD (at least 1 of the following): \>=25% IgM increase in serum IgM with \>=500 mg/dL increase from nadir (lowest serum IgM value at any time from baseline), confirmation needed if IgM was sole PD criterion; new lymph nodes \>1.5 cm, \>=50% increase in nadir in sum of product of diameters; 50% increase in longest diameter of previously identified node \>1 cm in short axis; new splenomegaly; new extranodal disease; new/recurrent bone marrow involvement; new symptomatic disease (pleural effusion, Bing Neel syndrome, amyloidosis, light chain deposition, paraprotein mediated disorder).
Time frame: From day of first dose (Day 1) until PD or death (up to 49.3 months)
Overall Survival (OS)
Overall survival was measured from the date of first dose to the date of the participant's death from any cause.
Time frame: From day of first dose (Day 1) until death due to any cause (up to 49.3 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Grade 3 or Higher TEAEs
An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were defined as AEs occurring after the first dose of study drugs and within 30 days following the last dose of study drug or initiation of subsequent antineoplastic treatment, whichever occurred earlier. TEAEs were graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 as Grade 1= Mild; Grade 2= Moderate; Grade 3= Severe; Grade 4= Life-threatening and Grade 5= Death. Number of participants with TEAEs and Grade 3 or higher TEAEs (included serious and non-serious events) were reported in this outcome measure.
Time frame: From start of the treatment (Day 1) up to 30 days after last dose or initiation of subsequent antineoplastic treatment, whichever occurred first (Day 1 up to 45.9 months)
Plasma Concentration of Ibrutinib
Plasma concentrations of ibrutinib were reported.
Time frame: Pre-dose on Day 1 of Weeks 1, 5 and 9