Waldenstrom MacroglobulinemiaPhase 4NCT04042376
A Study of Ibrutinib (PCI-32765) in Chinese Participants With Relapse or Refractory Waldenstrom's Macroglobulinemia (WM)
A Phase 4 study testing Ibrutinib in people with Waldenstrom Macroglobulinemia, run by Janssen Research & Development, LLC at 6 sites in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenstrom Macroglobulinemia
- What is being tested?
- Ibrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 6 sitesChina
- Study dates
- 18 Dec 2019to 19 Mar 2024
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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)
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
China6 sites
The First Hospital of Jilin University
Changchun, 130021
First affiliated Hospital of Zhejiang University
Hangzhou, 310003
Institute of Hematology and Blood Diseases Hospital
Tianjin, 300320
Wuhan Union Hospital
Wuhan, 430023
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an, 710004
Henan Cancer Hospital
Zhengzhou, 450008
About this study
Official title: 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.
- Conditions
- Waldenstrom Macroglobulinemia
- Being tested
- Ibrutinib
- 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 JNJ-54179060, PCI-32765
Ibrutinib will be administered orally, once daily, at a dose of 420 mg (140 mg*3 capsules taken together at one time).
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib 420 milligram (mg) | Experimental | 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. Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From start of the treatment (Day 1) up to 49.3 months
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Pre-dose on Day 1 of Weeks 1, 5 and 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2019
- Study start18 Dec 2019
- Primary completion19 Mar 2024
- Study completion19 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Waldenstrom MacroglobulinemiaStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04042376
- Sponsor's protocol ID
- CR108654
- Other IDs
- 54179060WAL4001
- Status last verified
- May 2025
- First submitted
- 31 Jul 2019
- Last updated
- 25 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- 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
Publications
Yi S, Cai Z, Hu Y, He A, Gao S, Li Q, Sha L, Zhang N, Ren Y, Gai X, Yang X, Qin R, Qiu L. Ibrutinib Efficacy, Safety, and Pharmacokinetics in Chinese Patients with Relapsed or Refractory Waldenstrom's Macroglobulinemia: A Multicenter, Single-Arm, Phase 4 Study. Adv Ther. 2024 Feb;41(2):672-685. doi: 10.1007/s12325-023-02720-w. Epub 2023 Dec 11.
PubMed 38079089
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04042376
- Acronym / sponsor ID
- CR108654
- Conditions
- Waldenstrom Macroglobulinemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2019 (actual)
- Primary completion
- 19 Mar 2024 (actual)
- Study completion
- 19 Mar 2024 (actual)
- First posted
- 1 Aug 2019 (actual)
- Results
- Posted 16 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib 420 milligram (mg) | Experimental | Drug: IbrutinibParticipants will receive ibrutinib 420 mg once daily, continuously starting at Day 1 of Week 1 until disease progression or unacceptable toxicity, whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: JNJ-54179060, PCI-32765Ibrutinib will be administered orally, once daily, at a dose of 420 mg (140 mg*3 capsules taken together at one time). | Drug | Ibrutinib 420 milligram (mg) |
Primary outcome
Overall Response Rate (ORR)
Time frame: From start of the treatment (Day 1) up to 49.3 months
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.
8 secondary outcomes
Clinical Response Rate (CRR)
Time frame: From start of the treatment (Day 1) up to 49.3 months
Very Good Partial Response (VGPR) or Better Response Rate
Time frame: From start of the treatment (Day 1) up to 49.3 months
Duration of Response (DOR)
Time frame: 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)
Time frame: From start of the treatment up to first documentation of PR or better (Day 1 up to 49.3 months)
Progression Free Survival (PFS)
Time frame: From day of first dose (Day 1) until PD or death (up to 49.3 months)
Overall Survival (OS)
Time frame: 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
Time frame: 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
Time frame: Pre-dose on Day 1 of Weeks 1, 5 and 9
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38079089Yi S, Cai Z, Hu Y, He A, Gao S, Li Q, Sha L, Zhang N, Ren Y, Gai X, Yang X, Qin R, Qiu L. Ibrutinib Efficacy, Safety, and Pharmacokinetics in Chinese Patients with Relapsed or Refractory Waldenstrom's Macroglobulinemia: A Multicenter, Single-Arm, Phase 4 Study. Adv Ther. 2024 Feb;41(2):672-685. doi: 10.1007/s12325-023-02720-w. Epub 2023 Dec 11.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ibrutinib in people with Waldenstrom Macroglobulinemia, run by Janssen Research & Development, LLC at 6 sites in China.
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 8 inclusion and 22 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 6 sites in China. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 16 Apr 2025). 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) (time frame: From start of the treatment (Day 1) up to 49.3 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 NCT04042376, which also lists 1 linked publication.
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.