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

Sponsor
Janssen Pharmaceutical K.K. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04062448
Collaborator
(none)
16
Enrollment
9
Locations
1
Arm
44.2
Anticipated Duration (Months)
1.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 2 Study of Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765) in Combination With Rituximab, in Japanese Patients With Waldenstrom's Macroglobulinemia (WM)
Actual Study Start Date :
Sep 25, 2019
Actual Primary Completion Date :
Aug 24, 2021
Anticipated Study Completion Date :
Jun 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ibrutinib + Rituximab

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
Ibrutinib 420 mg will be administered orally.
Other Names:
  • PCI-32765

    • Drug: Rituximab
    Rituximab 375 mg/m^2 will be administered intravenously.

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) - Assessed by Independent Review Committee (IRC) [Up to 3.7 years]

      The ORR is defined as the percentage of participants with complete response (CR), very good partial response (VGPR) or partial response (PR) by IRC assessment.

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) [Up to 3.7 years]

      PFS is defined as duration from the date of initial dose of ibrutinib to the date of disease progression or death, whichever occurs first.

    2. Pharmacokinetics (PK) of Ibrutinib and its Metabolite PCI-45227 [Day 1 of Week 4]

      Plasma concentration of ibrutinib and its metabolite PCI-45227 will be reported.

    3. Prognostic Biomarkers Relative to Disease and/or Treatment [Predose (Week 1)]

      Blood samples will be collected for biomarker analysis that may include myeloid differentiation primary response gene 88 (MYD88), and C-X-C chemokine receptor type 4 (CXCR-4), thought to be prognostic of disease and/or treatment.

    4. Number of Participants with Adverse Events [Up to 3.7 years]

      An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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

    Exclusion Criteria:

    • 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

    • Lactating or pregnant

    • Male participants who plan to father a child while enrolled in this study or within 3 months after the last dose of ibrutinib, and within 12 months after last dose of rituximab

    • Any contraindication to ibrutinib or rituximab including hypersensitivity to the active substance or to any of the excipients of ibrutinib or rituximab per local prescribing information

    • Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before the planned first dose of study intervention or is currently enrolled in an investigational study

    • Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg [for example], compromise the wellbeing) or that could prevent, limit, or confound the protocol-specified assessments

    • Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Kameda General Hospital Chiba Japan 296-8602
    2 National Cancer Center Hospital Chuo-Ku Japan 104-0045
    3 National Hospital Organization Kumamoto Medical Center Kumamoto-City Japan 860-0008
    4 Matsuyama Red Cross Hospital Matsuyama-City Japan 790-8524
    5 Nagoya City University Hospital Nagoya-City Japan 467-8602
    6 Osaka Metropolitan University Hospital Osaka Japan 545-8586
    7 Osaka University Hospital Suita-City Japan 565-0871
    8 National Hospital Organization Disaster Medical Center Tachikawa Japan 190-0014
    9 University of Tsukuba Hospital Tsukuba-City Japan 305-8576

    Sponsors and Collaborators

    • Janssen Pharmaceutical K.K.

    Investigators

    • Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Pharmaceutical K.K.
    ClinicalTrials.gov Identifier:
    NCT04062448
    Other Study ID Numbers:
    • CR108666
    • 54179060WAL2002
    First Posted:
    Aug 20, 2019
    Last Update Posted:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Additional relevant MeSH terms:
    Waldenstrom Macroglobulinemia
    Rituximab

    Study Results

    No Results Posted as of Aug 12, 2022