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)

Chronic Lymphocytic Leukemia (CLL) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05105841
• Other study ID #: M20-353
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 8, 2021
• Est. completion date: September 20, 2025

Study information

• Verified date: August 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: September 20, 2025
• Est. primary completion date: September 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia (CLL)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Small Lymphocytic Lymphoma (SLL)

Intervention

Drug:
• Venetoclax
Oral Tablet
• Ibrutinib
Oral Capsule
• Obinutuzumab
Intravenous (IV) Infusion

Locations

Country	Name	City	State
Japan	Hyogo Prefectural Amagasaki General Medical Center /ID# 234082	Amagasaki-shi	Hyogo
Japan	Chiba Cancer Center /ID# 238839	Chiba-shi	Chiba
Japan	National Cancer Center Hospital /ID# 232449	Chuo-ku	Tokyo
Japan	Kyushu University Hospital /ID# 238437	Fukuoka-shi	Fukuoka
Japan	Tokai University Hospital /ID# 238970	Isehara-shi	Kanagawa
Japan	Shimane University Hospital /ID# 234076	Izumo-shi	Shimane
Japan	The Cancer Institute Hospital Of JFCR /ID# 232450	Koto-ku	Tokyo
Japan	University Hospital Kyoto Prefectural University of Medicine /ID# 239883	Kyoto-shi	Kyoto
Japan	National Hospital Organization Shikoku Cancer Center /ID# 234059	Matsuyama-shi	Ehime
Japan	Aichi Cancer Center Hospital /ID# 238797	Nagoya-shi	Aichi
Japan	Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital /ID# 233524	Nagoya-shi	Aichi
Japan	NHO Nagoya Medical Center /ID# 233523	Nagoya-shi	Aichi
Japan	Niigata University Medical & Dental Hospital /ID# 238324	Niigata-shi	Niigata
Japan	Okayama University Hospital /ID# 238467	Okayama-shi	Okayama
Japan	Kindai University Hospital /ID# 234001	Osakasayama-shi	Osaka
Japan	Hokkaido University Hospital /ID# 238377	Sapporo-shi	Hokkaido
Japan	Tohoku University Hospital /ID# 238433	Sendai-shi	Miyagi
Japan	Jichi Medical University Hospital /ID# 238434	Shimotsuke-shi	Tochigi
Japan	Osaka University Hospital /ID# 234037	Suita-shi	Osaka
Japan	Yamagata University Hospital /ID# 234032	Yamagata-shi	Yamagata

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Related info