A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT03462719
• Date of registration: 06/03/2018
• Prospective Registration: Yes
• Primary sponsor: Janssen Research & Development, LLC
• Public title: A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) GLOW
• Scientific title: A Randomized, Open-label, Phase 3 Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Subjects With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL).
• Date of first enrolment: April 17, 2018
• Target sample size: 211
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03462719
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Belgium, Canada, Czechia, Denmark, France, Israel, Netherlands, Poland, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: Janssen Research & Development, LLC Clinical Trial
• Affiliation: Janssen Research & Development, LLC

Key inclusion & exclusion criteria

Inclusion Criteria:

- Adult participants who are: (a) greater than or equal to (>=) 65 years old or, (b) 18
to 64 years old and have at least 1 of the following:

1. Cumulative Illness Rating Scale (CIRS) score > 6

2. Creatinine clearance (CrCl) estimated less than (<) 70 milliliter per minute
(mL/min) using Cockcroft-Gault equation

- Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
that meets International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

- Measurable nodal disease (by computed tomography [CT]), defined as at least one lymph
node > 1.5 centimeter (cm) in longest diameter

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade less than or
equal to (<=) 2

- Active CLL/SLL requiring treatment per the iwCLL criteria

Exclusion Criteria:

- Prior anti-leukemic therapy for CLL or SLL

- Presence of deletion of the short arm of chromosome 17 (del17p) or known TP53 mutation
detected at a threshold of >10 percent (%) variable allele frequency (VAF)

- Major surgery within 4 weeks of first dose of study treatment

- Known bleeding disorders (example, von Willebrand's disease or hemophilia)

- Central nervous system (CNS) involvement or suspected Richter's syndrome



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Leukemia, Lymphocytic, Chronic, B-Cell

Intervention(s)

Drug: Venetoclax

Drug: Chlorambucil

Drug: Ibrutinib

Drug: Ibrutinib (as Subsequent Therapy)

Drug: Obinutuzumab

Primary Outcome(s)

Progression Free Survival (PFS) [Time Frame: Up to 2 years 10 months]

Secondary Outcome(s)

Duration of Response (DOR) [Time Frame: Up to 2 years 10 months]

Plasma Concentration of Ibrutinib and Venetoclax [Time Frame: Ibrutinib: Pre-dose-Day 1 of Cycles 2, 3, 5 and 6 (each cycle is defined as 28 days), Venetoclax: Pre-dose-Day 1 of Cycles 5 and 6]

Complete Response Rate (CRR) [Time Frame: Up to 2 years 10 months]

Overall Response Rate (ORR) [Time Frame: Up to 2 years 10 months]

Number of Participants With Abnormal Clinical Laboratory Findings [Time Frame: Up to 4 years 10 months]

Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability [Time Frame: Up to 4 years 10 months]

Overall Survival (OS) [Time Frame: Up to 4 years 10 months]

Time to Worsening as Measured by Using EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L) [Time Frame: Up to 2 years 10 months]

Time to Worsening Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30) [Time Frame: Up to 2 years 10 months]

Minimal Residual Disease (MRD) Negative Rate [Time Frame: Up to 2 years 10 months]

Percentage of Participants With Sustained Platelet Improvement [Time Frame: Up to 2 years 10 months]

Percentage of Participants With Sustained Hemoglobin Improvement [Time Frame: Up to 2 years 10 months]

Time to Worsening and Time to Improvement as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score [Time Frame: Up to 2 years 10 months]

Time-to-Next Treatment [Time Frame: Up to 2 years 10 months]

Secondary ID(s)

CR108428

2017-004699-77

54179060CLL3011

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Pharmacyclics LLC.

Results

• Results available: Yes
• Date Posted: 28/03/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03462719