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

JRCT ID: jRCT2080224857

Registered date:06/09/2019

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: Waldenstrom Macroglobulinemia
• Date of first enrollment: 08/10/2019
• Target sample size: 14
• Countries of recruitment: Japan
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : Ibrutinib
INN of investigational material : Ibrutinib
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Ibrutinib 420 mg will be administered orally.

control material(s)
Generic name etc : Rituximab
INN of investigational material : Rituximab
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Rituximab 375 mg/m^2 will be administered intravenously.

Outcome(s)

Primary Outcome

efficacy
Overall Response Rate (ORR) - Assessed by Independent Review Committee (IRC)

Up to 3.7 years

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

efficacy
Progression Free Survival (PFS)

Up to 3.7 years

PFS is defined as duration from the date of initial dose of ibrutinib to the date of disease progression or death, whichever occurs first.
pharmacokinetics
Pharmacokinetics (PK) of Ibrutinib and its Metabolite PCI-45227

Day 1 of Week 4

Plasma concentration of ibrutinib and its metabolite PCI-45227 will be reported.
exploratory
Prognostic Biomarkers Relative to Disease and/or Treatment

Predose (Week 1)

Blood samples will be collected for biomarker analysis that may include myeloid differentiation primary response gene 88 (MYD88), and CX-C chemokine receptor type 4 (CXCR-4), thought to be prognostic of disease and/or treatment.
safety
Number of Participants with Adverse Events

Up to 3.7 years

An adverse event is any untoward medical event that occurs in participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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 naive 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 months 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

Exclude 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 enrollmentt

- 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 Information

• Primary Sponsor: Janssen Pharmaceutical K.K.
• Secondary Sponsor: -
• Source(s) of Monetary Support: -
• Secondary ID(s): NCT04062448,JapicCTI-194941