Clinical trial · Interventional
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)
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).
NCT03462719CI-TRIAL-00124654GLOWactive not recruitingPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 29, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260929-000001
Summary
Brief summary (as posted)
The purpose of this study is to assess progression-free survival (PFS) from treatment with ibrutinib plus venetoclax (I+VEN) compared with obinutuzumab plus chlorambucil (G-Clb) as assessed by an Independent Review Committee (IRC).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Leukemia, Lymphocytic, Chronic, B-Cell | Chronic Lymphocytic Leukemia | ALIAS | 0.90 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Chlorambucil | Drug | Chlorambucil | ALIAS |
| Ibrutinib | Drug | Ibrutinib | ALIAS |
| Ibrutinib (as Subsequent Therapy) | Drug | Ibrutinib | ALIAS |
| Obinutuzumab | Drug | Obinutuzumab | ALIAS |
| Venetoclax | Drug | Venetoclax | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Treatment Arm A: Ibrutinib and Venetoclax (I+VEN)
- description
- Participants will initially receive ibrutinib (420 mg \[milligrams\]/day) for 3 cycles. Venetoclax dose ramp up (from 20 to 400 mg over 5 weeks) will begin at Cycle 4 and the combination of ibrutinib and venetoclax will be given for 12 cycles (each cycle is equivalent to 28 days). Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity.
- interventionNames
- Drug: Ibrutinib
- Drug: Venetoclax
- Drug: Ibrutinib (as Subsequent Therapy)
- type
- ACTIVE_COMPARATOR
- label
- Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb)
- description
- Participants will receive chlorambucil and obinutuzumab (G-Clb) for 6 cycles. Participants will receive obinutuzumab, 1000 mg intravenously (IV) on Days 1, 8 and 15 of Cycle 1, and on Day 1 of Cycles 2 to 6 and chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight, on Days 1 and 15 of Cycles 1 to 6. Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (3)
- DERIVEDKater AP, Owen C, Moreno C, Follows G, Munir T, Levin MD, Benjamini O, Janssens A, Osterborg A, Robak T, Simkovic M, Stevens D, Voloshin S, Vorobyev V, Ysebaert L, Qin R, Steele AJ, Schuier N, Baeten K, Caces DB, Niemann CU. Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities. NEJM Evid. 2022 Jul;1(7):EVIDoa2200006. doi: 10.1056/EVIDoa2200006. Epub 2022 May 13. PMID 38319255
- DERIVEDNiemann CU, Munir T, Moreno C, Owen C, Follows GA, Benjamini O, Janssens A, Levin MD, Robak T, Simkovic M, Voloshin S, Vorobyev V, Yagci M, Ysebaert L, Qi K, Qi Q, Sinet P, Parisi L, Srinivasan S, Schuier N, Baeten K, Howes A, Caces DB, Kater AP. Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1423-1433. doi: 10.1016/S1470-2045(23)00452-7. Epub 2023 Nov 6. PMID 37944541
- DERIVEDMoreno C, Solman IG, Tam CS, Grigg A, Scarfo L, Kipps TJ, Srinivasan S, Mali RS, Zhou C, Dean JP, Szafer-Glusman E, Choi M. Immune restoration with ibrutinib plus venetoclax in first-line chronic lymphocytic leukemia: the phase 2 CAPTIVATE study. Blood Adv. 2023 Sep 26;7(18):5294-5303. doi: 10.1182/bloodadvances.2023010236. PMID 37315225