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

Waldenstrom Macroglobulinemia Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT04062448
• Other study ID #: CR108666
• Secondary ID: 54179060WAL2002
• Status: Completed
• Phase: Phase 2
• Start date: September 25, 2019
• Est. completion date: March 2, 2023

Study information

• Verified date: March 2024
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 2, 2023
• Est. primary completion date: August 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Waldenstrom Macroglobulinemia

Intervention

Drug:
• Ibrutinib
Ibrutinib 420 mg will be administered orally.
• Rituximab
Rituximab 375 mg/m^2 will be administered intravenously.

Locations

Country	Name	City	State
Japan	Kameda General Hospital	Chiba
Japan	National Cancer Center Hospital	Chuo-Ku
Japan	National Hospital Organization Kumamoto Medical Center	Kumamoto City
Japan	Matsuyama Red Cross Hospital	Matsuyama-City
Japan	Nagoya City University Hospital	Nagoya-City
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Osaka University Hospital	Suita-City
Japan	National Hospital Organization Disaster Medical Center	Tachikawa
Japan	University of Tsukuba Hospital	Tsukuba-City

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 1 year 11 months
Secondary	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.	From the date of initial dose up to 3 years and 5 months
Secondary	Plasma Concentrations of Ibrutinib	Plasma concentrations of ibrutinib were reported.	Day 1 of Week 4: Predose, 1 hour, 2 hours, 4 hours, and 6 hours postdose
Secondary	Plasma Concentrations of Metabolite PCI-45227	Plasma concentrations of metabolite PCI-45227 were reported.	Day 1 of Week 4: Predose, 1 hour, 2 hours, 4 hours, and 6 hours postdose
Secondary	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.	Day 1 of Week 1
Secondary	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.	Day 1 of Week 1
Secondary	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.	From first dose of study drug up to 30 days post last dose of study drug (that is, up to 40.6 months)