Clinical trial NCT04477486: 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
Official title: Phase 2 Study of the Efficacy and Safety of Venetoclax in Combination With Ibrutinib in Japanese Subjects With Relapsed/Refractory Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Mantle Cell Lymphoma (MCL)
Keywords: MCL
Venetoclax
ABT-199
Ibrutinib
Imbruvica
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-07-20
Enrollment: 13
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Achieving Best Overall Response of Complete Response (CR), as Assessed by the Independent Review Committee (IRC)
timeFrame: Week 13
Secondary outcomes:
measure: Percentage of Participants Achieving Best Overall Response of CR or PR, as Assessed by the IRC
timeFrame: Week 104
measure: Percentage of Participants Achieving Best Overall Response of CR as Assessed by the Investigator
timeFrame: Week 104
measure: Percentage of Participants Achieving Best Overall Response of CR or PR, as Assessed by the Investigator
timeFrame: Week 104
measure: Duration of Response (DOR) for Participants Who Achieved a Best Overall Response of CR or PR, as Assessed by the Investigator
timeFrame: Week 104
measure: DOR for Participants Who Achieved a Best Overall Response of CR or PR, as Assessed by the IRC
timeFrame: Week 104
measure: Undetectable Minimal Residual Disease (uMRD) in Participants Who Achieve a Best Overall Response of CR as Assessed by the Investigator.
timeFrame: Week 104
measure: uMRD in Participants Who Achieve a Best Overall Response of CR as Assessed by IRC.
timeFrame: Week 104
measure: Progression-Free Survival (PFS)
timeFrame: Week 104
measure: Overall Survival (OS)
timeFrame: Week 104
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
facility: NHO Nagoya Medical Center /ID# 221958
state: Aichi
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital /ID# 221565
state: Aichi
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital /ID# 223299
state: Fukuoka
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital /ID# 221662
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Kobe City Medical Center General Hospital /ID# 221744
state: Hyogo
city: Higashi Ibaraki-gun
country: Japan
facility: National Hospital Organization Mito Medical Center /ID# 224912
state: Ibaraki
city: Kanazawa-shi
country: Japan
facility: Ishikawa Prefectural Central Hospital /ID# 224896
state: Ishikawa
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital /ID# 221975
state: Miyagi
city: Okayama-shi
country: Japan
facility: Duplicate_Okayama University Hospital /ID# 221623
state: Okayama
city: Kawagoe-shi
country: Japan
facility: Saitama Medical Center /ID# 224910
state: Saitama
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 221812
state: Tokyo
city: Yamagata-shi
country: Japan
facility: Yamagata University Hospital /ID# 221573
state: Yamagata
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: