Clinical trial NCT04042376: A Study of Ibrutinib (PCI-32765) in Chinese Participants With Relapse or Refractory Waldenstrom's Macroglobulinemia (WM)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Waldenstrom Macroglobulinemia
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-08-01
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 participants with relapsed or refractory waldenstrom's macroglobulinemia.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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)

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From start of the treatment (Day 1) up to 49.3 months
Secondary outcomes:
measure: Clinical Response Rate (CRR)
timeFrame: From start of the treatment (Day 1) up to 49.3 months
measure: Very Good Partial Response (VGPR) or Better Response Rate
timeFrame: From start of the treatment (Day 1) up to 49.3 months
measure: Duration of Response (DOR)
timeFrame: From the date of first documented response up to date of first documented PD or death (Day 1 up to 49.3 months)
measure: Time to Response (TTR)
timeFrame: From start of the treatment up to first documentation of PR or better (Day 1 up to 49.3 months)
measure: Progression Free Survival (PFS)
timeFrame: From day of first dose (Day 1) until PD or death (up to 49.3 months)
measure: Overall Survival (OS)
timeFrame: From day of first dose (Day 1) until death due to any cause (up to 49.3 months)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Grade 3 or Higher TEAEs
timeFrame: 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)
measure: Plasma Concentration of Ibrutinib
timeFrame: Pre-dose on Day 1 of Weeks 1, 5 and 9
Other outcomes:
Locations:
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Hangzhou
country: China
facility: First affiliated Hospital of Zhejiang University
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: