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Waldenstrom MacroglobulinemiaPhase 2NCT04062448

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

A Phase 2 study testing Ibrutinib and Rituximab in people with Waldenstrom Macroglobulinemia, run by Janssen Pharmaceutical K.K. at 9 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Waldenstrom Macroglobulinemia
What is being tested?
Ibrutinib and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
9 sitesJapan
Study dates
25 Sep 2019to 2 Mar 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Japan9 sites

  • Kameda Medical Center

    Chiba, 296-8602

  • National Cancer Center Hospital

    Chūōku, 104 0045

  • National Hospital Organization Kumamoto Medical Center

    Kumamoto, 860 0008

  • Matsuyama Red Cross Hospital

    Matsuyama, 790-8524

  • Nagoya City University Hospital

    Nagoya, 467 8602

  • Osaka Metropolitan University Hospital

    Osaka, 545 8586

  • Osaka University Hospital

    Suita, 565-0871

  • National Hospital Organization Disaster Medical Center

    Tachikawa, 190-0014

  • University of Tsukuba Hospital

    Tsukuba, 305 8576

Other trials in Japan

About this study

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)

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).

Being tested
Ibrutinib, Rituximab
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    Also called PCI-32765

    Ibrutinib 420 mg will be administered orally.

  • RituximabDrug

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

Study groups in NCT04062448
Study groupRoleWhat they receive
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.
Receives: Drug: Ibrutinib; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 1 year 11 months

Secondary outcomes (6)

  1. Progression Free Survival (PFS) Assessed by Independent Review Committee

    PFS was defined as duration from the date of initial dose of ibrutinib to the date of first documented evidence of disease progression or death, whichever occurred first regardless of the use of subsequent antineoplastic therapy prior to documented disease progression or death. Kaplan-Meier method was used for the analysis.

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

  2. Plasma Concentrations of Ibrutinib

    Plasma concentrations of ibrutinib were reported.

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

  3. Plasma Concentrations of Metabolite PCI-45227

    Plasma concentrations of metabolite PCI-45227 were reported.

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

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

    Number of participants with MYD88 biomarker mutations were reported. MYD88 was assessed using next generation sequencing to detect the somatic mutations in the bone marrow aspiration samples collected during the study.

    Measured: Day 1 of Week 1

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

    Number of participants with CXCR-4 biomarker mutations were reported. CXCR-4 was assessed using next generation sequencing to detect the somatic mutations in the bone marrow aspiration samples collected during the study.

    Measured: Day 1 of Week 1

  6. Number of Participants With Treatment- Emergent Adverse Events (TEAEs)

    An adverse event was defined as any untoward medical event that occurred in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were defined as any AE that occurred at or after the initial administration of study intervention through the day of last dose plus 30 days.

    Measured: From first dose of study drug up to 30 days post last dose of study drug (that is, up to 40.6 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2019
  2. Study start25 Sep 2019
  3. Primary completion24 Aug 2021
  4. Study completion2 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04062448
Sponsor's protocol ID
CR108666
Other IDs
54179060WAL2002
Status last verified
May 2025
First submitted
19 Aug 2019
Last updated
25 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib and Rituximab in people with Waldenstrom Macroglobulinemia, run by Janssen Pharmaceutical K.K. at 9 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) According to the Modified Sixth International Workshop on Waldenstrom's Macroglobulinemia (IWWM) Criteria (time frame: Up to 1 year 11 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04062448.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.

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