Clinical trial NCT05105841: 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)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Keywords: Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Ibrutinib
Imbruvica
Venetoclax
Venclexta
Venclyxto
Obinutuzumab
GA101
Gazyva
RO5072759
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2021-11-03
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: Up to Week 32
measure: CR/CRi Rate, as Assessed by an IRC per iwCLL for Venetoclax + Ibrutinib (V+I)
timeFrame: Up to Week 56
Secondary outcomes:
measure: CR/CRi Rate, as Assessed by an Investigator per iwCLL for (V+G)
timeFrame: Up to Week 32
measure: CR/CRi Rate, as Assessed by an Investigator per iwCLL for (V+I)
timeFrame: Up to Week 56
measure: Overall response rate (ORR) as Assessed by IRC for (V+G)
timeFrame: Up to Week 32
measure: ORR as Assessed by IRC (V+I)
timeFrame: Up to Week 56
measure: ORR as Assessed by Investigator for (V+G)
timeFrame: Up to Week 32
measure: ORR Assessed by Investigator + Ibrutinib (V+I)
timeFrame: Up to Week 56
measure: Progression-Free Survival (PFS) as Assessed by IRC for (V+G)
timeFrame: Up to Week 32
measure: PFS as Assessed by IRC for (V+I)
timeFrame: Up to Week 56
measure: PFS as Assessed by Investigator for (V+G)
timeFrame: Up to Week 32
measure: PFS as Assessed by Investigator for (V+I)
timeFrame: Up to Week 56
measure: Duration of response (DOR) as Assessed by IRC for (V+G)
timeFrame: Up to Week 32
measure: DOR as Assessed by IRC for (V+I)
timeFrame: Up to Week 56
measure: DOR as Assessed by Investigator for (V+G)
timeFrame: Up to Week 32
measure: DOR as Assessed by Investigator for (V+I)
timeFrame: Up to Week 56
measure: Overall Survival (OS) for (V+G)
timeFrame: Up to Week 32
measure: OS for (V+I)
timeFrame: Up to Week 56
measure: Time to progression (TTP) as Assessed by IRC for (V+G)
timeFrame: Up to Week 32
measure: TTP as Assessed by IRC for (V+I)
timeFrame: Up to Week 56
measure: TTP as Assessed by Investigator for (V+G)
timeFrame: Up to Week 32
measure: TTP as Assessed by Investigator for (V+I)
timeFrame: Up to Week 56
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
facility: NHO Nagoya Medical Center /ID# 233523
state: Aichi
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital /ID# 238797
state: Aichi
city: Nagoya-shi
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital /ID# 233524
state: Aichi
city: Chiba-shi
country: Japan
facility: Duplicate_Chiba Cancer Center /ID# 238839
state: Chiba
city: Matsuyama-shi
country: Japan
facility: National Hospital Organization Shikoku Cancer Center /ID# 234059
state: Ehime
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital /ID# 238437
state: Fukuoka
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital /ID# 238377
state: Hokkaido
city: Amagasaki-shi
country: Japan
facility: Hyogo Prefectural Amagasaki General Medical Center /ID# 234082
state: Hyogo
city: Isehara
country: Japan
facility: Tokai University Hospital- Isehara Campus /ID# 238970
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine /ID# 239883
state: Kyoto
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital /ID# 238433
state: Miyagi
city: Niigata-shi
country: Japan
facility: Niigata University Medical & Dental Hospital /ID# 238324
state: Niigata
city: Okayama-shi
country: Japan
facility: Duplicate_Okayama University Hospital /ID# 238467
state: Okayama
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital /ID# 234001
state: Osaka
city: Suita-shi
country: Japan
facility: Osaka University Hospital /ID# 234037
state: Osaka
city: Izumo-shi
country: Japan
facility: Shimane University Hospital /ID# 234076
state: Shimane
city: Shimotsuke-shi
country: Japan
facility: Jichi Medical University Hospital /ID# 238434
state: Tochigi
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 232449
state: Tokyo
city: Koto
country: Japan
facility: The Cancer Institute Hospital Of JFCR /ID# 232450
state: Tokyo
city: Yamagata-shi
country: Japan
facility: Yamagata University Hospital /ID# 234032
state: Yamagata
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: