A Study of Ibrutinib (PCI-32765) in Chinese Participants With Relapse or Refractory Waldenstrom's Macroglobulinemia (WM)

A Single Arm, Multicenter, Phase 4 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765) in Chinese Subjects With Relapse or Refractory Waldenström's Macroglobulinemia

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 Overview

• Status: Completed
• Conditions: Waldenstrom Macroglobulinemia
• Intervention / Treatment: Drug: Ibrutinib

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Hangzhou, China, 310003
    • First Affiliated Hospital of Zhejiang University
  • Tianjin, China, 300320
    • Institute of Hematology and Blood Diseases Hospital
  • Wuhan, China, 430023
    • Wuhan Union Hospital
  • Xi'an, China, 710004
    • The Second Affiliated Hospital of Xi'an Jiaotong University
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibrutinib 420 milligram (mg); 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.	Drug: Ibrutinib; Ibrutinib will be administered orally, once daily, at a dose of 420 mg (140 mg*3 capsules taken together at one time).; Other Names: PCI-32765; JNJ-54179060

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From start of the treatment (Day 1) up to 49.3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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).	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.	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).	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.	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.	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.	Pre-dose on Day 1 of Weeks 1, 5 and 9

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2019
• Primary Completion (Actual): March 19, 2024
• Study Completion (Actual): March 19, 2024

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 1, 2019

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Waldenstrom Macroglobulinemia; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Ibrutinib
• Other Study ID Numbers: CR108654; 54179060WAL4001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes