A Study of Ibrutinib in Combination With Rituximab, in Japanese Participants With Waldenstrom's Macroglobulinemia (WM)

NCT04062448 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CR10866654179060WAL2002
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to evaluate overall response rate (ORR) by Independent Review Committee (IRC) assessment, when combined with rituximab in Japanese participants with treatment naïve or relapsed/refractory Waldenstrom's Macroglobulinemia (WM).

Conditions

Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) According to the Modified Sixth International Workshop on Waldenstrom's Macroglobulinemia (IWWM) Criteria

  ORR is defined as the percentage of participants achieving a best overall response of confirmed complete response (CR), very good partial response (VGPR) or partial response (PR) according to the modified sixth IWWM criteria (National Comprehensive Cancer Network \[NCCN\] version 2, 2019), as assessed by the Independent Review Committee (IRC). CR: Immunoglobulin M (IgM) in normal range, disappearance of monoclonal protein by immunofixation, no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (if present at baseline) along with no signs or symptoms attributable to Waldenstrom's Macroglobulinemia (WM); VGPR and PR: greater than or equal to (\>=) 90 percent (%) (for VGPR) and \>=50% (for PR) reduction of serum IgM, decrease in adenopathy/organomegaly (if present at baseline) on physical examination or computerized tomography (CT) scan, no new symptoms or signs of active disease.

  Up to 1 year 11 months

Secondary Outcomes (6)

• Progression Free Survival (PFS) Assessed by Independent Review Committee

  From the date of initial dose up to 3 years and 5 months

• Plasma Concentrations of Ibrutinib

  Day 1 of Week 4: Predose, 1 hour, 2 hours, 4 hours, and 6 hours postdose

• Plasma Concentrations of Metabolite PCI-45227

  Day 1 of Week 4: Predose, 1 hour, 2 hours, 4 hours, and 6 hours postdose

• Number of Participants With Myeloid Differentiation Primary Response Gene 88 (MYD88) Biomarker Mutation

  Day 1 of Week 1

• Number of Participants With C-X-C Chemokine Receptor Type 4 (CXCR-4) Biomarker Mutations

  Day 1 of Week 1

Study Arms (1)

Ibrutinib + Rituximab

EXPERIMENTAL

Participants will receive ibrutinib 420 milligram (mg) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity in combination with rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 of Weeks 1 to 4 and Weeks 17 to 20.

Drug: Ibrutinib; Drug: Rituximab

Interventions

Ibrutinib DRUG

Ibrutinib 420 mg will be administered orally.

Also known as: PCI-32765

Ibrutinib + Rituximab

Rituximab DRUG

Rituximab 375 mg/m\^2 will be administered intravenously.

Ibrutinib + Rituximab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia (WM) in accordance with the consensus panel of the second International Workshop on Waldenstrom's Macroglobulinemia (IWWM)
• Japanese participants with treatment naïve or relapsed/refractory WM
• Measurable disease defined as serum monoclonal immunoglobulin M (IgM) greater than (\>) 0.5 gram per deciliter (g/dL)
• Symptomatic disease, requiring treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (\<=) 2
• 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. Women of childbearing potential must be practicing a highly effective, preferably user independent method of birth control during treatment with any drug in this study and for up to 12 months after the last dose of rituximab, 1 month after last dose of ibrutinib. Male participants must use an effective barrier method of contraception during the study and after receiving the last dose of ibrutinib, and for up to 12 months after last dose of rituximab if sexually active with a female of childbearing potential
• Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. Participants must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
• Must be willing and able to adhere to the lifestyle restrictions specified in this protocol

You may not qualify if:

• Involvement of the central nervous system by WM
• Prior exposure to ibrutinib or other Bruton's Tyrosine Kinase (BTK) inhibitors
• Rituximab treatment within the last 12 months before the first dose of study intervention
• Received any WM-related therapy \<=30 days prior to first administration of study treatment
• Plasmapheresis less than (\<) 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
• 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
• Currently active, clinically significant Child-Pugh Class B or C hepatic impairment
• Inability or difficulty swallowing capsules, malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function
• Stroke or intracranial hemorrhage within 12 months prior to enrollment
• Currently active, clinically significant cardiovascular disease
• Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
• Infection with human immunodeficiency virus (HIV) or active infection with hepatitis B or hepatitis C virus
• Major surgery within 4 weeks of first dose of study drug

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (9)

Kameda Medical Center

Chiba, 296-8602, Japan

Location

National Cancer Center Hospital

Chūōku, 104 0045, Japan

Location

National Hospital Organization Kumamoto Medical Center

Kumamoto, 860 0008, Japan

Location

Matsuyama Red Cross Hospital

Matsuyama, 790-8524, Japan

Location

Nagoya City University Hospital

Nagoya, 467 8602, Japan

Location

Osaka Metropolitan University Hospital

Osaka, 545 8586, Japan

Location

Osaka University Hospital

Suita, 565-0871, Japan

Location

National Hospital Organization Disaster Medical Center

Tachikawa, 190-0014, Japan

Location

University of Tsukuba Hospital

Tsukuba, 305 8576, Japan

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

ibrutinib; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Director
• Organization: Janssen Pharmaceutical K.K.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Pharmaceutical K.K., Japan Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 20, 2019
• Study Start: September 25, 2019
• Primary Completion: August 24, 2021
• Study Completion: March 2, 2023
• Last Updated: May 25, 2025
• Results First Posted: December 1, 2022

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

JP (9)