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

AbbVie13 enrolled

Overview

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. Symptoms of MCL may include enlarged lymph nodes, stomach pain, fever, night sweats, and weight loss. Currently, MCL is not curable with standard therapies. 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.

Safety and efficacy data through 09 February 2022 are included in the interim analysis.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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.

Locations (12)

NHO Nagoya Medical Center /ID# 221958

Nagoya, Aichi-ken, Japan

Aichi Cancer Center Hospital /ID# 221565

Nagoya, Aichi-ken, Japan

Kyushu University Hospital /ID# 223299

Fukuoka, Fukuoka, Japan

Hokkaido University Hospital /ID# 221662

Sapporo, Hokkaido, Japan

Kobe City Medical Center General Hospital /ID# 221744

Kobe, Hyōgo, Japan

National Hospital Organization Mito Medical Center /ID# 224912

Higashi Ibaraki-gun, Ibaraki, Japan

Ishikawa Prefectural Central Hospital /ID# 224896

Kanazawa, Ishikawa-ken, Japan

Tohoku University Hospital /ID# 221975

Sendai, Miyagi, Japan

Duplicate_Okayama University Hospital /ID# 221623

Okayama, Okayama-ken, Japan

Saitama Medical Center /ID# 224910

Kawagoe-shi, Saitama, Japan

...and 2 more locations

Outcomes

Primary Outcomes

Percentage of Participants Achieving Best Overall Response of Complete Response (CR), as Assessed by the Independent Review Committee (IRC)

Complete response rate (CRR), defined as the percentage of participants achieving a best overall response of complete response (CR) per the Revised Criteria for Response Assessment for Malignant Lymphoma following the Lugano classification (Cheson 2014), assessed by an Independent Review Committee (IRC).

Time frame: Week 13

Secondary Outcomes

Percentage of Participants Achieving Best Overall Response of CR or PR, as Assessed by the IRC

Overall Response Rate (ORR), defined as the percentage of participants with a best overall response of CR or PR, per the Revised Criteria for Response Assessment for Malignant Lymphoma, assessed by an Independent Review Committee (IRC).

Time frame: Week 104

Percentage of Participants Achieving Best Overall Response of CR 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 for Malignant Lymphoma .

Time frame: Week 104

Percentage of Participants Achieving Best Overall Response of CR or PR, as Assessed by the Investigator

Best overall response of CR or PR will be evaluated using 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 for Malignant Lymphoma, as assessed by the investigator.

Time frame: Week 104

Duration of Response (DOR) for Participants Who Achieved a Best Overall Response of CR or PR, 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 for Malignant Lymphoma, as assessed by the investigator.

Time frame: Week 104

DOR for Participants Who Achieved a Best Overall Response of CR or PR, as Assessed by the IRC

Time frame: Week 104

Undetectable Minimal Residual Disease (uMRD) in Participants Who Achieve a Best Overall Response of CR as Assessed by the Investigator.

MRD rate is defined as the percentage of participants with uMRD who achieve a best overall response of CR, according to the Revised Criteria for Response Assessment for Malignant Lymphoma, as assessed by the investigator.

Time frame: Week 104

uMRD in Participants Who Achieve a Best Overall Response of CR as Assessed by IRC.

Time frame: Week 104

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 for Malignant Lymphoma, or death from any cause, whichever occurs first.

Time frame: Week 104

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.

Time frame: Week 104

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

Overview

Conditions

Interventions

Eligibility

Locations (12)

Outcomes

Primary Outcomes

Secondary Outcomes