Study to Assess Effect of Oral Venetoclax Tablet in Combination With Oral Ibrutinib Capsule on Best Overall Response of Complete Response in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma

Study Overview
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Brief Summary
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Mantle Cell Lymphoma (MCL) is a form of Non-Hodgkin Lymphoma (NHL - cancer of the lymphatic system in blood) where cells from outer edge of the lymph nodes, called mantle zone become cancerous. In Japan, MCL accounts for about 3% of all NHL cases. Some symptoms of MCL are enlarged lymph nodes, stomach pain, fever, night sweats, and weight loss. MCL is not curable with standard therapies and has poor outcomes. The purpose of this study is to evaluate the safety, efficacy and effect of venetoclax in combination with ibrutinib on best overall response of complete response in participants with relapsed (return of disease) or refractory (not responding to treatment) (R/R) MCL. Venetoclax is an investigational drug being developed for the treatment of MCL. Ibrutinib is a drug approved for the treatment of MCL. Participants will receive venetoclax (increasing doses) and ibrutinib (fixed dose) for approximately 104 weeks, followed by ibrutinib alone. Adult participants with R/R MCL will be enrolled. Around 12 participants will be enrolled in Japan. Participants will receive oral venetoclax tablet and oral ibrutinib capsule for 104 weeks. After 104 weeks, participants will receive ibrutinib once daily until their disease progresses, or they cannot tolerate the medication, or until they do not want to participate in the study. There may be a higher treatment burden for participants in this study compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, bone marrow biopsies, checking for side effects, and completing questionnaires.

Official Title
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Phase 2 Study of the Efficacy and Safety of Venetoclax in Combination With Ibrutinib in Japanese Subjects With Relapsed/Refractory Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma (MCL)

Intervention / Treatment
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* Drug: Ibrutinib
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed Mantle Cell Lymphoma (MCL) (tumor tissue) by local testing. At least 1 measurable site of disease on cross-sectional imaging that is >= 2.0 centimeters (cm) in the longest diameter and measurable in 2 perpendicular dimensions per Computed Tomography (CT). At least 1, but no more than 5, prior treatment regimens for MCL including at least 1 prior rituximab/anti-CD20 containing regimen. Failure to achieve at least partial response (PR) with, or documented disease progression after, the most recent treatment regimen. Exclusion Criteria: Prior therapy with ibrutinib or other Bruton Tyrosine Kinase (BTK) inhibitors. History of other malignancies, except: Malignancy treated with curative intent and with no known active disease present for >= 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated carcinoma in situ without evidence of disease. History or current evidence of central nervous system lymphoma. Treatment with any of the following within 7 days prior to the first dose of study drug: Moderate or strong cytochrome P450 3A (CYP3A) inhibitors. Moderate or strong CYP3A inducers. Anticancer therapy, including chemotherapy, radiotherapy, small molecule, and investigational agents, and/or monoclonal antibody <=21 days prior to the first dose of study drug.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibrutinib + Venetoclax<br>Participants will receive Ibrutinib Dose A + Venetoclax in various doses until a target dose is reached, for up to 104 weeks, followed by Ibrutinib monotherapy. | Drug: Ibrutinib<br>* Capsule; Oral<br>* Other names: Imbruvica;Drug: Venetoclax<br>* Tablet; Oral<br>* Other names: Venclyxto;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Best Overall Response of Complete Response (CR), as assessed by the Independent Review Committee (IRC) | Best overall response of CR is evaluated using the complete response rate (CRR), defined as the percentage of participants achieving a best overall response of CR for the venetoclax and ibrutinib combination, per the Revised Criteria for Response Assessment as assessed by the Independent Review Committee (IRC). | At Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Best Overall Response of Complete Response (CR) or Partial Response (PR), as assessed by the IRC | Best Overall Response of CR or PR will be evaluated using Overall Response Rate (ORR). The ORR is defined as the percentage of participants with a best overall response of CR or PR, according to the Revised Criteria for Response Assessment, as assessed by the IRC. | Up to Approximately 2 Years | 
| Percentage of Participants Achieving Best Overall Response of Complete Response as assessed by the Investigator | Best overall response of CR is defined as the percentage of participants achieving a best overall response of CR for the venetoclax and ibrutinib combination, as assessed by the investigator per the Revised Criteria for Response Assessment. | Up to Approximately 2 Years | 
| Percentage of Participants Achieving Best Overall Response of Complete Response (CR) or Partial Response (PR), as assessed by the Investigator | Best Overall Response of CR or PR will be evaluated using Overall Response Rate (ORR). The ORR is defined as the percentage of participants with a best overall response of CR or PR, according to the Revised Criteria for Response Assessment, as assessed by the investigator. | Up to Approximately 2 Years | 
| Percentage of Participants Achieving Duration of Response (DOR) for a Best Overall Response, as assessed by the Investigator | DOR is defined as the time from the first occurrence of response (CR or PR) to disease progression or death, whichever occurs first, according to the Revised Criteria for Response Assessment, as assessed by the investigator. | Up to Approximately 2 Years | 
| Percentage of Participants Achieving Duration of Response (DOR) for a Best Overall Response, as assessed by the IRC | DOR is defined as the time from the first occurrence of response (CR or PR) to disease progression or death, whichever occurs first, according to the Revised Criteria for Response Assessment, as assessed by the Independent Review Committee (IRC). | Up to Approximately 2 Years | 
| Percentage of Participants Achieving an Undetectable Minimal Residual Disease (MRD) who Achieve a Best Overall Response, as assessed by the Investigator | MRD rate is defined as the percentage of participants with undetectable MRD who achieve a best overall response of CR, according to the Revised Criteria for Response Assessment, as assessed by the investigator. | Up to Approximately 2 Years | 
| Percentage of Participants Achieving Undetectable Minimal Residual Disease (MRD) in Participants who Achieve a Best Overall Response of CR, as assessed by the IRC | MRD rate is defined as the percentage of participants with undetectable MRD who achieve a best overall response of CR, according to the Revised Criteria for Response Assessment, as assessed by the IRC. | Up to Approximately 2 Years | 
| Progression-Free Survival (PFS) | PFS is defined as the time from the date of the first dose of study drug (venetoclax or ibrutinib) to the date of investigator-assessed disease progression, using the Revised Response Criteria for Response Assessment of Malignant Lymphoma, or death from any cause, whichever occurs first. | Up to Approximately 2 Years | 
| Overall Survival (OS) | OS is defined as the time from the date of the first dose of the study drug (venetoclax or ibrutinib) to death from any cause. | Up to Approximately 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MCL, Venetoclax, ABT-199, Ibrutinib, Imbruvica