A Study of Ibrutinib (PCI-32765) in Chinese Participants With Relapse or Refractory Waldenstrom's Macroglobulinemia (WM)
- Registration Number
- NCT04042376
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
- Men and women greater than or equal to (>=) 18 years of age
- Eastern Cooperative Oncology Group (ECOG) less than or equal to (<=) 2
- Previously received at least one prior therapy for WM and have had either documented disease progression or had no response to the most recent treatment regimen
- Centrally confirmed clinicopathological diagnosis of WM
- Measurable disease defined as serum monoclonal immunoglobulin M (IgM) >0.5 gram per deciliter (g/dL)
- Symptomatic disease, requiring treatment
- Hematology and biochemical values within protocol-defined limits
- Female participants of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception while taking study drug. Female participants of childbearing potential should avoid becoming pregnant while taking ibrutinib and for up to 1 month after the last dose of study drug. Male participants must use an effective barrier method of contraception during the study and for 3 months following the last dose of ibrutinib if sexually active with a female of childbearing potential
- Involvement of the central nervous system by WM
- Evidence of disease transformation
- Prior exposure to BTK inhibitors
- Known hypersensitivity reaction to ibrutinib or to the excipients in its formulation
- Received any WM-related therapy <=30 days prior to first administration of study treatment
- Received a prior allogeneic hematopoietic stem cell transplant
- Plasmapheresis <35 days prior to the initiation of study drug, except when at least one serum IgM central assessment was performed during the screening period and was >35 days from the most recent plasmapheresis procedure
- History of other malignancies, except: (a) malignancy treated with curative intent and with no known active disease present for >=2 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician; (b) adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease; (c) adequately treated carcinoma in situ without evidence of disease
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
- Infection requiring systemic treatment that was completed <=14 days before the first dose of study drug
- Bleeding disorders or hemophilia
- Stroke or intracranial hemorrhage within 6 months prior to enrollment
- Infection with human immunodeficiency virus (HIV) or active infection with hepatitis B or hepatitis C
- Major surgery within 4 weeks of first dose of study drug
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the participant's safety or put the study outcomes at undue risk
- Currently active, clinically significant hepatic impairment Child-Pugh Class B or C according to the Child Pugh classification
- Currently active, clinically significant cardiovascular disease
- Requires or receiving anticoagulation with warfarin or other Vitamin K antagonists
- Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
- Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
- Lactating or pregnant
- Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local participant privacy regulations)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ibrutinib 420 milligram (mg) Ibrutinib Participants will receive ibrutinib 420 mg once daily, continuously starting at Day 1 of Week 1 until disease progression or unacceptable toxicity, whichever occurs first.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) From start of the treatment (Day 1) up to 49.3 months 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.
- Secondary Outcome Measures
Name Time Method Clinical Response Rate (CRR) From start of the treatment (Day 1) up to 49.3 months 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.
Very Good Partial Response (VGPR) or Better Response Rate From start of the treatment (Day 1) up to 49.3 months 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.
Duration of Response (DOR) From the date of first documented response up to date of first documented PD or death (Day 1 up to 49.3 months) 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).
Time to Response (TTR) From start of the treatment up to first documentation of PR or better (Day 1 up to 49.3 months) 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.
Progression Free Survival (PFS) From day of first dose (Day 1) until PD or death (up to 49.3 months) 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).
Overall Survival (OS) From day of first dose (Day 1) until death due to any cause (up to 49.3 months) Overall survival was measured from the date of first dose to the date of the participant's death from any cause.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Grade 3 or Higher TEAEs 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) 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.
Plasma Concentration of Ibrutinib Pre-dose on Day 1 of Weeks 1, 5 and 9 Plasma concentrations of ibrutinib were reported.
Trial Locations
- Locations (6)
Wuhan Union Hospital
🇨🇳Wuhan, China
The Second Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
The First Hospital of Jilin University
🇨🇳Changchun, China
Institute of Hematology and Blood Diseases Hospital
🇨🇳Tianjin, China
First affiliated Hospital of Zhejiang University
🇨🇳Hangzhou, China