Clinical Trials /

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

NCT04062448

Description:

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).

Related Conditions:
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CR108666
  • SECONDARY ID: 54179060WAL2002
  • NCT ID: NCT04062448

Conditions

  • Waldenstrom Macroglobulinemia

Interventions

DrugSynonymsArms
IbrutinibPCI-32765Ibrutinib + Rituximab
RituximabIbrutinib + Rituximab

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Ibrutinib + RituximabExperimentalParticipants 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.
  • Ibrutinib
  • Rituximab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR) - Assessed by Independent Review Committee (IRC)
Time Frame:Up to 3.7 years
Safety Issue:
Description: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

Measure:Progression Free Survival (PFS)
Time Frame:Up to 3.7 years
Safety Issue:
Description:PFS is defined as duration from the date of initial dose of ibrutinib to the date of disease progression or death, whichever occurs first.
Measure:Pharmacokinetics (PK) of Ibrutinib and its Metabolite PCI-45227
Time Frame:Day 1 of Week 4
Safety Issue:
Description:Plasma concentration of ibrutinib and its metabolite PCI-45227 will be reported.
Measure:Prognostic Biomarkers Relative to Disease and/or Treatment
Time Frame:Predose (Week 1)
Safety Issue:
Description: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.
Measure:Number of Participants with Adverse Events
Time Frame:Up to 3.7 years
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Pharmaceutical K.K.

Last Updated

June 18, 2020