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
- Conditions
- Mantle Cell Lymphoma (MCL)
- Interventions
- Registration Number
- NCT04477486
- Lead Sponsor
- AbbVie
- Brief Summary
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.
- Detailed Description
Safety and efficacy data through 09 February 2022 are included in the interim analysis.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 13
- 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.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ibrutinib + Venetoclax Venetoclax 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. Ibrutinib + Venetoclax Ibrutinib 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Best Overall Response of Complete Response (CR), as Assessed by the Independent Review Committee (IRC) Week 13 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).
- Secondary Outcome Measures
Name Time Method uMRD in Participants Who Achieve a Best Overall Response of CR as Assessed by IRC. Week 104 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 IRC.
Progression-Free Survival (PFS) Week 104 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.
Overall Survival (OS) Week 104 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.
Percentage of Participants Achieving Best Overall Response of CR or PR, as Assessed by the IRC Week 104 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).
Percentage of Participants Achieving Best Overall Response of CR as Assessed by the Investigator Week 104 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 .
Percentage of Participants Achieving Best Overall Response of CR or PR, as Assessed by the Investigator Week 104 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.
Duration of Response (DOR) for Participants Who Achieved a Best Overall Response of CR or PR, as Assessed by the Investigator Week 104 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.
DOR for Participants Who Achieved a Best Overall Response of CR or PR, as Assessed by the IRC Week 104 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 IRC.
Undetectable Minimal Residual Disease (uMRD) in Participants Who Achieve a Best Overall Response of CR as Assessed by the Investigator. Week 104 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.
Trial Locations
- Locations (12)
Duplicate_Okayama University Hospital /ID# 221623
🇯🇵Okayama-shi, Okayama, Japan
NHO Nagoya Medical Center /ID# 221958
🇯🇵Nagoya-shi, Aichi, Japan
Aichi Cancer Center Hospital /ID# 221565
🇯🇵Nagoya-shi, Aichi, Japan
Kyushu University Hospital /ID# 223299
🇯🇵Fukuoka-shi, Fukuoka, Japan
Hokkaido University Hospital /ID# 221662
🇯🇵Sapporo-shi, Hokkaido, Japan
Kobe City Medical Center General Hospital /ID# 221744
🇯🇵Kobe-shi, Hyogo, Japan
National Hospital Organization Mito Medical Center /ID# 224912
🇯🇵Higashi Ibaraki-gun, Ibaraki, Japan
Ishikawa Prefectural Central Hospital /ID# 224896
🇯🇵Kanazawa-shi, Ishikawa, Japan
Tohoku University Hospital /ID# 221975
🇯🇵Sendai-shi, Miyagi, Japan
Saitama Medical Center /ID# 224910
🇯🇵Kawagoe-shi, Saitama, Japan
National Cancer Center Hospital /ID# 221812
🇯🇵Chuo-ku, Tokyo, Japan
Yamagata University Hospital /ID# 221573
🇯🇵Yamagata-shi, Yamagata, Japan