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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)

Phase 2
Active, not recruiting
Conditions
Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Interventions
Registration Number
NCT05105841
Lead Sponsor
AbbVie
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
20
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Venetoclax + Obinutuzumab (V+G)VenetoclaxParticipants will receive venetoclax + obinutuzumab for twelve 28-day cycles.
Venetoclax + Obinutuzumab (V+G)ObinutuzumabParticipants will receive venetoclax + obinutuzumab for twelve 28-day cycles.
Venetoclax + Ibrutinib (V+I)VenetoclaxParticipants will receive venetoclax + ibrutinib for fifteen 28-day cycles.
Venetoclax + Ibrutinib (V+I)IbrutinibParticipants will receive venetoclax + ibrutinib for fifteen 28-day cycles.
Primary Outcome Measures
NameTimeMethod
CR/CRi Rate, as Assessed by an IRC per iwCLL for Venetoclax + Ibrutinib (V+I)Up to Week 56

CR rate is defined as the percentage of participants achieving a best response of CR or CRi.

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)Up to Week 32

CR rate is defined as the percentage of participants achieving a best response of CR or CRi.

Secondary Outcome Measures
NameTimeMethod
CR/CRi Rate, as Assessed by an Investigator per iwCLL for (V+G)Up to Week 32

CR rate is defined as the percentage of participants achieving a best response of CR or CRi.

CR/CRi Rate, as Assessed by an Investigator per iwCLL for (V+I)Up to Week 56

CR rate is defined as the percentage of participants achieving a best response of CR or CRi.

Overall response rate (ORR) as Assessed by IRC for (V+G)Up to Week 32

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.

ORR as Assessed by IRC (V+I)Up to Week 56

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.

Progression-Free Survival (PFS) as Assessed by IRC for (V+G)Up to Week 32

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.

DOR as Assessed by IRC for (V+I)Up to Week 56

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.

TTP as Assessed by Investigator for (V+I)Up to Week 56

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.

ORR as Assessed by Investigator for (V+G)Up to Week 32

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.

Duration of response (DOR) as Assessed by IRC for (V+G)Up to Week 32

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.

DOR as Assessed by Investigator for (V+G)Up to Week 32

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.

DOR as Assessed by Investigator for (V+I)Up to Week 56

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.

Overall Survival (OS) for (V+G)Up to Week 32

OS is defined as the time from the date of the first dose of any study drug until death due to any cause.

OS for (V+I)Up to Week 56

OS is defined as the time from the date of the first dose of any study drug until death due to any cause.

Time to progression (TTP) as Assessed by IRC for (V+G)Up to Week 32

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.

TTP as Assessed by IRC for (V+I)Up to Week 56

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.

ORR Assessed by Investigator + Ibrutinib (V+I)Up to Week 56

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.

TTP as Assessed by Investigator for (V+G)Up to Week 32

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.

PFS as Assessed by IRC for (V+I)Up to Week 56

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.

PFS as Assessed by Investigator for (V+G)Up to Week 32

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.

PFS as Assessed by Investigator for (V+I)Up to Week 56

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.

Trial Locations

Locations (20)

National Cancer Center Hospital /ID# 232449

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Chuo-ku, Tokyo, Japan

University Hospital Kyoto Prefectural University of Medicine /ID# 239883

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Kyoto-shi, Kyoto, Japan

Tohoku University Hospital /ID# 238433

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Sendai-shi, Miyagi, Japan

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital /ID# 233524

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Nagoya-shi, Aichi, Japan

The Cancer Institute Hospital Of JFCR /ID# 232450

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Koto, Tokyo, Japan

Kindai University Hospital /ID# 234001

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Osakasayama-shi, Osaka, Japan

National Hospital Organization Shikoku Cancer Center /ID# 234059

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Matsuyama-shi, Ehime, Japan

Hokkaido University Hospital /ID# 238377

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Sapporo-shi, Hokkaido, Japan

Niigata University Medical & Dental Hospital /ID# 238324

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Niigata-shi, Niigata, Japan

Duplicate_Okayama University Hospital /ID# 238467

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Okayama-shi, Okayama, Japan

Shimane University Hospital /ID# 234076

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Izumo-shi, Shimane, Japan

Osaka University Hospital /ID# 234037

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Suita-shi, Osaka, Japan

Jichi Medical University Hospital /ID# 238434

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Shimotsuke-shi, Tochigi, Japan

NHO Nagoya Medical Center /ID# 233523

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Nagoya-shi, Aichi, Japan

Duplicate_Chiba Cancer Center /ID# 238839

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Chiba-shi, Chiba, Japan

Aichi Cancer Center Hospital /ID# 238797

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Nagoya-shi, Aichi, Japan

Kyushu University Hospital /ID# 238437

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Fukuoka-shi, Fukuoka, Japan

Tokai University Hospital- Isehara Campus /ID# 238970

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Isehara, Kanagawa, Japan

Hyogo Prefectural Amagasaki General Medical Center /ID# 234082

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Amagasaki-shi, Hyogo, Japan

Yamagata University Hospital /ID# 234032

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Yamagata-shi, Yamagata, Japan

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