Chronic Lymphocytic Leukemia (CLL)Phase 2NCT05105841
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 testing Venetoclax, Ibrutinib and Obinutuzumab in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by AbbVie at 20 sites in Japan.
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%). Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
- What is being tested?
- Venetoclax, Ibrutinib and Obinutuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 20 sitesJapan
- Study dates
- 8 Nov 2021to 9 Oct 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Japan20 sites
Hyogo Prefectural Amagasaki General Medical Center /ID# 234082
Amagasaki-shi, Hyōgo, 660-8550
Chiba Cancer Center /ID# 238839
Chiba, Chiba, 260-8717
National Cancer Center Hospital /ID# 232449
Chuo-ku, Tokyo, 104-0045
Kyushu University Hospital /ID# 238437
Fukuoka, Fukuoka, 812-8582
Tokai University Hospital /ID# 238970
Isehara, Kanagawa, 259-1193
Shimane University Hospital /ID# 234076
Izumo-shi, Shimane, 693-8501
The Cancer Institute Hospital Of JFCR /ID# 232450
Koto-ku, Tokyo, 135-8550
University Hospital Kyoto Prefectural University of Medicine /ID# 239883
Kyoto, Kyoto, 602-8566
National Hospital Organization Shikoku Cancer Center /ID# 234059
Matsuyama, Ehime, 791-0280
NHO Nagoya Medical Center /ID# 233523
Nagoya, Aichi-ken, 460-0001
Aichi Cancer Center Hospital /ID# 238797
Nagoya, Aichi-ken, 464-8681
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital /ID# 233524
Nagoya, Aichi-ken, 466-8650
Niigata University Medical & Dental Hospital /ID# 238324
Niigata, Niigata, 951-8520
Okayama University Hospital /ID# 238467
Okayama, Okayama-ken, 700-8558
Kindai University Hospital /ID# 234001
Sakai-shi, Osaka, 590-0197
Hokkaido University Hospital /ID# 238377
Sapporo, Hokkaido, 060-8648
Tohoku University Hospital /ID# 238433
Sendai, Miyagi, 9808574
Jichi Medical University Hospital /ID# 238434
Shimotsuke-shi, Tochigi, 329-0498
Osaka University Hospital /ID# 234037
Suita-shi, Osaka, 565-0871
Yamagata University Hospital /ID# 234032
Yamagata, Yamagata, 990-9585
About this study
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)
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.
Read more
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.
- Being tested
- Venetoclax, Ibrutinib, Obinutuzumab
- Keywords
- Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Ibrutinib, Imbruvica, Venetoclax, Venclexta, Venclyxto, Obinutuzumab, GA101, Gazyva, RO5072759
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Also called Venclexta, ABT-199, GDC-0199
Oral Tablet
IbrutinibDrug
Also called Imbruvica
Oral Capsule
ObinutuzumabDrug
Also called GA101, Gazyva, RO5072759
Intravenous (IV) Infusion
| Study group | Role | What they receive |
|---|---|---|
| Venetoclax + Obinutuzumab (V+G) | Experimental | Participants will receive venetoclax + obinutuzumab for twelve 28-day cycles. Receives: Drug: Venetoclax; Drug: Obinutuzumab |
| Venetoclax + Ibrutinib (V+I) | Experimental | Participants will receive venetoclax + ibrutinib for fifteen 28-day cycles. Receives: Drug: Venetoclax; Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission (CR) and CR With an Incomplete Marrow Recovery (CRi) Rate Per Independent Review Committee (IRC)
CR+CRi rate was defined as the percentage of participants achieving a best response of CR or CRi as assessed by an IRC per 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for tumor response.
CR required all of the following:
- Group A:
- Lymphadenopathy: None > 1.5 centimeters
- Blood Lymphocytes: <4,000/microliter (μL)
- Hepatomegaly: None
- Splenomegaly: None
- Marrow: Normocellular, < 30% lymphocytes, no B-lymphoid nodules
- Group B:
- Platelet Count: > 100,000/μL
- Hemoglobin: > 11.0 grams per deciliter (g/dL)
- Neutrophils: > 1500/μL
CRi was defined as a CR with peripheral cytopenia and incomplete recovery of the bone marrow, manifested by persistent cytopenias.
Measured: Up to 46 months
Secondary outcomes (10)
CR+CRi Rate Per Investigator Assessment
CR+CRi rate was defined as the percentage of participants achieving a best response of CR or CRi as assessed by an IRC per iwCLL criteria for tumor response.
CR required all of the following:
- Group A:
- Lymphadenopathy: None > 1.5 centimeters
- Blood Lymphocytes: <4,000/μL
- Hepatomegaly: None
- Splenomegaly: None
- Marrow: Normocellular, < 30% lymphocytes, no B-lymphoid nodules
- Group B:
- Platelet Count: > 100,000/μL
- Hemoglobin: > 11.0 g/dL
- Neutrophils: > 1500/μL
CRi was defined as a CR with peripheral cytopenia and incomplete recovery of the bone marrow, manifested by persistent cytopenias.
Measured: Up to 46 months
Overall Response Rate (ORR) Per IRC
ORR was defined as the percentage of participants with a best overall response of CR, CRi, partial remission (PR) or nodular partial remission (nPR) per 2008 iwCLL criteria.
PR required at Least 2 Criteria from Group A AND at least 1 Criterion from Group B:
- Group A:
- Lymphadenopathy: Decrease ≥ 50%
- Blood Lymphocytes: Decrease ≥ 50% from baseline
- Hepatomegaly: Decrease ≥ 50%
- Splenomegaly: Decrease ≥ 50%
- Marrow: 50% reduction in marrow infiltrate or B-lymphoid nodules
- Group B:
- Platelet Count: > 100,000/μL or increase ≥ 50% over baseline
- Hemoglobin: > 11.0 g/dL or increase ≥ 50% over baseline
- Neutrophils: > 1500/μL or increase ≥ 50% over baseline nPR was a response that met the criteria for CR, but the bone marrow biopsy showed lymphoid nodules, reflecting residual disease.
Measured: Baseline up to 46 months
ORR Per Investigator Assessment
ORR was defined as the percentage of participants with a best overall response of CR, CRi, PR or nPR per 2008 iwCLL criteria.
Measured: Baseline up to 46 months
Progression-Free Survival (PFS) Per IRC
PFS was 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 occurred first, according to iwCLL criteria. PFS was analyzed using Kaplan-Meier methodology.
Measured: Up to 46 months
PFS Per Investigator Assessment
PFS was 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 occurred first, according to iwCLL criteria. PFS was analyzed using Kaplan-Meier methodology.
Measured: Up to 46 months
Duration of Response (DOR) as Assessed by IRC
DOR was 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 occurred first, as determined by an IRC according to iwCLL criteria.
Measured: Up to 46 months
DOR as Assessed by Investigator
DOR was 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 occurred first, as determined by an IRC according to iwCLL criteria.
Measured: Up to 46 months
Overall Survival (OS)
OS was defined as the time from the date of the first dose of any study drug until death due to any cause.
Measured: Up to 46 months
Time to Progression (TTP) as Assessed by IRC
TTP was 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.
Measured: Up to 46 months
TTP as Assessed by Investigator
TTP was 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.
Measured: Up to 46 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2021
- Study start8 Nov 2021
- Primary completion9 Oct 2025
- Study completion9 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Lymphocytic Leukemia (CLL)Studies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05105841
- Sponsor's protocol ID
- M20-353
- Status last verified
- Sep 2026
- First submitted
- 25 Oct 2021
- Last updated
- 21 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
- Expanded access
- Available