Study to Assess Change in Disease Activity and Adverse Events of Oral Venetoclax in Combination With Intravenous (IV) Obinutuzumab or Oral Ibrutinib in Adult Participants With Untreated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

A Phase 2 Study of the Safety and Efficacy of Venetoclax in Combination With Obinutuzumab or Ibrutinib in Japanese Subjects With Previously Untreated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, representing approximately 30% of all adult leukemias. There is a large difference in proportion of malignant lymphoma between the United States (US) and Japan was seen in CLL/small lymphocytic lymphoma (SLL) (Japan, 3.2%; US, 24.1%). The purpose of this study is to assess how well venetoclax works in combination with obinutuzumab (V+G, Cohort 1) or with ibrutinib (V+I, Cohort 2) in Japanese participants with previously untreated CLL/Small Lymphocytic Lymphoma (SLL). Adverse events and change in disease activity will be assessed.

Venetoclax is an approved drug for the treatment of CLL and SLL. Study doctors put the participants in 1 of 2 groups, called treatment arms, based on variable alternating assignment. Approximately 20 adult participants with previously untreated CLL/SLL will be enrolled in the study in approximately 20 sites in Japan.

Participants in group 1 will receive oral venetoclax + intravenous (IV) obinutuzumab (V+G) in 28-day cycles for a total of 12 cycles, and participants in group 2 will receive oral venetoclax + oral ibrutinib (V+I) in 28-day cycles for a total of 15 cycles.

There may be higher treatment burden for participants in this trial 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, and checking for side effects.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)
• Intervention / Treatment: Drug: Venetoclax; Drug: Obinutuzumab; Drug: Ibrutinib

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 460-0001
      • NHO Nagoya Medical Center /ID# 233523
    • Nagoya-shi, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital /ID# 238797
    • Nagoya-shi, Aichi, Japan, 466-8650
      • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital /ID# 233524
  • Chiba
    • Chiba-shi, Chiba, Japan, 260-8717
      • Chiba Cancer Center /ID# 238839
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center /ID# 234059
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 238437
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital /ID# 238377
  • Hyogo
    • Amagasaki-shi, Hyogo, Japan, 660-8550
      • Hyogo Prefectural Amagasaki General Medical Center /ID# 234082
  • Kanagawa
    • Isehara-shi, Kanagawa, Japan, 259-1193
      • Tokai University Hospital /ID# 238970
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • University Hospital Kyoto Prefectural University of Medicine /ID# 239883
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 9808574
      • Tohoku University Hospital /ID# 238433
  • Niigata
    • Niigata-shi, Niigata, Japan, 951-8520
      • Niigata University Medical & Dental Hospital /ID# 238324
  • Okayama
    • Okayama-shi, Okayama, Japan, 700-8558
      • Okayama University Hospital /ID# 238467
  • Osaka
    • Osakasayama-shi, Osaka, Japan, 589-8511
      • Kindai University Hospital /ID# 234001
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital /ID# 234037
  • Shimane
    • Izumo-shi, Shimane, Japan, 693-8501
      • Shimane University Hospital /ID# 234076
  • Tochigi
    • Shimotsuke-shi, Tochigi, Japan, 329-0498
      • Jichi Medical University Hospital /ID# 238434
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 232449
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital Of JFCR /ID# 232450
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 990-9585
      • Yamagata University Hospital /ID# 234032

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult male or female, at least ≥ 65 years old; or 20 to 64 years old and have at least 1 of the following:

  • Cumulative Illness Rating Scale (CIRS) score > 6.
  • Creatinine clearance (CrCl) estimated < 70 mL/min using Cockcroft-Gault equation.
• Must have measurable nodal disease (by computed tomography [CT]), defined as at least one lymph node > 1.5 cm in longest diameter.
• Diagnosed Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) that requires treatment according to the Modified 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.

Exclusion Criteria:

• Transformation of Chronic Lymphocytic Leukemia (CLL) to aggressive non-Hodgkin lymphoma (NHL; Richter's transformation or pro-lymphocytic leukemia).
• Previous treatment history for CLL/SLL.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venetoclax + Obinutuzumab (V+G); Participants will receive venetoclax + obinutuzumab for twelve 28-day cycles.	Drug: Venetoclax; Oral Tablet; Other Names: Venclexta; ABT-199; GDC-0199; Drug: Obinutuzumab; Intravenous (IV) Infusion; Other Names: Gazyva; RO5072759; GA101
Experimental: Venetoclax + Ibrutinib (V+I); Participants will receive venetoclax + ibrutinib for fifteen 28-day cycles.	Drug: Venetoclax; Oral Tablet; Other Names: Venclexta; ABT-199; GDC-0199; Drug: Ibrutinib; Oral Capsule; Other Names: Imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission (CR) with an Incomplete Marrow Recovery (CRi) Rate, as Assessed by an Independent Review Committee (IRC) per Modified 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) for Venetoclax + Obinutuzumab (V+G)	CR rate is defined as the percentage of participants achieving a best response of CR or CRi.	Up to Week 32
CR/CRi Rate, as Assessed by an IRC per iwCLL for Venetoclax + Ibrutinib (V+I)	CR rate is defined as the percentage of participants achieving a best response of CR or CRi.	Up to Week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR/CRi Rate, as Assessed by an Investigator per iwCLL for (V+G)	CR rate is defined as the percentage of participants achieving a best response of CR or CRi.	Up to Week 32
CR/CRi Rate, as Assessed by an Investigator per iwCLL for (V+I)	CR rate is defined as the percentage of participants achieving a best response of CR or CRi.	Up to Week 56
Overall response rate (ORR) as Assessed by IRC for (V+G)	ORR is defined as the proportion of participants with a best overall response of CR, CRi, partial remission (PR) or nodular partial remission (nPR) per 2008 iwCLL criteria as assessed by an IRC.	Up to Week 32
ORR as Assessed by IRC (V+I)	ORR is defined as the proportion of participants with a best overall response of CR, CRi, partial remission (PR) or nodular partial remission (nPR) per 2008 iwCLL criteria as assessed by an IRC.	Up to Week 56
ORR as Assessed by Investigator for (V+G)	ORR is defined as the proportion of participants with a best overall response of CR, CRi, partial remission (PR) or nodular partial remission (nPR) per 2008 iwCLL criteria as assessed by an investigator.	Up to Week 32
ORR Assessed by Investigator + Ibrutinib (V+I)	ORR is defined as the proportion of participants with a best overall response of CR, CRi, partial remission (PR) or nodular partial remission (nPR) per 2008 iwCLL criteria as assessed by an investigator.	Up to Week 56
Progression-Free Survival (PFS) as Assessed by IRC for (V+G)	PFS is defined as the time from the date of first dose of any study drug until the date of disease progression or death due to any cause, whichever occurs first, as determined by an IRC according to iwCLL criteria.	Up to Week 32
PFS as Assessed by IRC for (V+I)	PFS is defined as the time from the date of first dose of any study drug until the date of disease progression or death due to any cause, whichever occurs first, as determined by an IRC according to iwCLL criteria.	Up to Week 56
PFS as Assessed by Investigator for (V+G)	PFS is defined as the time from the date of first dose of any study drug until the date of disease progression or death due to any cause, whichever occurs first, as determined by an investigator according to iwCLL criteria.	Up to Week 32
PFS as Assessed by Investigator for (V+I)	PFS is defined as the time from the date of first dose of any study drug until the date of disease progression or death due to any cause, whichever occurs first, as determined by an investigator according to iwCLL criteria.	Up to Week 56
Duration of response (DOR) as Assessed by IRC for (V+G)	DOR is defined as the time from the first occurrence of overall response (CR, CRi, PR or nPR) until disease progression or death due to any cause, whichever occurs first, as determined by an IRC according to iwCLL criteria.	Up to Week 32
DOR as Assessed by IRC for (V+I)	DOR is defined as the time from the first occurrence of overall response (CR, CRi, PR or nPR) until disease progression or death due to any cause, whichever occurs first, as determined by an IRC according to iwCLL criteria.	Up to Week 56
DOR as Assessed by Investigator for (V+G)	DOR is defined as the time from the first occurrence of overall response (CR, CRi, PR or nPR) until disease progression or death due to any cause, whichever occurs first, as determined by an investigator according to iwCLL criteria.	Up to Week 32
DOR as Assessed by Investigator for (V+I)	DOR is defined as the time from the first occurrence of overall response (CR, CRi, PR or nPR) until disease progression or death due to any cause, whichever occurs first, as determined by an investigator according to iwCLL criteria.	Up to Week 56
Overall Survival (OS) for (V+G)	OS is defined as the time from the date of the first dose of any study drug until death due to any cause.	Up to Week 32
OS for (V+I)	OS is defined as the time from the date of the first dose of any study drug until death due to any cause.	Up to Week 56
Time to progression (TTP) as Assessed by IRC for (V+G)	TTP is defined as the time from the date of first dose of any study drug until the date of disease progression, as determined by an IRC according to iwCLL criteria.	Up to Week 32
TTP as Assessed by IRC for (V+I)	TTP is defined as the time from the date of first dose of any study drug until the date of disease progression, as determined by an IRC according to iwCLL criteria.	Up to Week 56
TTP as Assessed by Investigator for (V+G)	TTP is defined as the time from the date of first dose of any study drug until the date of disease progression, as determined by an investigator according to iwCLL criteria.	Up to Week 32
TTP as Assessed by Investigator for (V+I)	TTP is defined as the time from the date of first dose of any study drug until the date of disease progression, as determined by an investigator according to iwCLL criteria.	Up to Week 56

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related info

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2021
• Primary Completion (Estimated): September 20, 2025
• Study Completion (Estimated): September 20, 2025

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Ibrutinib; Venetoclax; Chronic Lymphocytic Leukemia (CLL); Venclexta; Obinutuzumab; GA101; Venclyxto; Small Lymphocytic Lymphoma (SLL); Gazyva; Imbruvica; RO5072759
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, B-Cell; Chronic Disease; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Antineoplastic Agents, Immunological; Venetoclax; Obinutuzumab
• Other Study ID Numbers: M20-353

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing 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/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes