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

NCT04477486 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: M20-075
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 12

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.

Conditions

Mantle Cell Lymphoma (MCL)

Keywords

MCL; Venetoclax; ABT-199; Ibrutinib; Imbruvica

Outcome Measures

Primary Outcomes (1)

• 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).

  Week 13

Secondary Outcomes (9)

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

  Week 104

• Percentage of Participants Achieving Best Overall Response of CR as Assessed by the Investigator

  Week 104

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

  Week 104

• Duration of Response (DOR) for Participants Who Achieved a Best Overall Response of CR or PR, as Assessed by the Investigator

  Week 104

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

  Week 104

Study Arms (1)

Ibrutinib + Venetoclax

EXPERIMENTAL

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; Drug: Venetoclax

Interventions

Ibrutinib DRUG

Capsule; Oral

Also known as: Imbruvica

Ibrutinib + Venetoclax

Venetoclax DRUG

Tablet; Oral

Also known as: ABT-199, Venclexta, GDC-0199, Venclyxto

Ibrutinib + Venetoclax

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (12)

NHO Nagoya Medical Center /ID# 221958

Nagoya, Aichi-ken, 460-0001, Japan

Location

Aichi Cancer Center Hospital /ID# 221565

Nagoya, Aichi-ken, 464-8681, Japan

Location

Kyushu University Hospital /ID# 223299

Fukuoka, Fukuoka, 812-8582, Japan

Location

Hokkaido University Hospital /ID# 221662

Sapporo, Hokkaido, 060-8648, Japan

Location

Kobe City Medical Center General Hospital /ID# 221744

Kobe, Hyōgo, 650-0047, Japan

Location

National Hospital Organization Mito Medical Center /ID# 224912

Higashi Ibaraki-gun, Ibaraki, 311-3193, Japan

Location

Ishikawa Prefectural Central Hospital /ID# 224896

Kanazawa, Ishikawa-ken, 920-8530, Japan

Location

Tohoku University Hospital /ID# 221975

Sendai, Miyagi, 9808574, Japan

Location

Duplicate_Okayama University Hospital /ID# 221623

Okayama, Okayama-ken, 700-8558, Japan

Location

Saitama Medical Center /ID# 224910

Kawagoe-shi, Saitama, 350-8550, Japan

Location

National Cancer Center Hospital /ID# 221812

Chuo-ku, Tokyo, 104-0045, Japan

Location

Yamagata University Hospital /ID# 221573

Yamagata, Yamagata, 990-9585, Japan

Location

Related Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinib; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 20, 2020
• Study Start: September 23, 2020
• Primary Completion: February 9, 2022
• Study Completion: May 28, 2025
• Last Updated: July 9, 2025
• Results First Posted: January 14, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

Locations

JP (12)