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)
Summary
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).
Timeline
- Start
- 2018-04-17
- Primary completion
- 2021-02-26
- Completion
- 2029-04-05
Outcome
Met primary endpoint
registry analysis (superiority test); Treatment Arm A (Ibrutinib + Venetoclax) vs Treatment Arm B (Chlorambucil + Obinutuzumab); p <0.0001; Hazard Ratio (HR) 0.216 (95% CI 0.131 to 0.357); Log Rank NCT03462719 ↗
paper PFS was significantly longer for ibrutinib-venetoclax than for chlorambucil-obinutuzumab (hazard ratio, 0.216; 95% confidence interval [CI], 0.131 to 0.357; P<0.001). PMID 38319255 ↗
release “Results from the GLOW study demonstrated how the fixed-duration, all-oral combination showed superior progression-free survival (PFS) compared to chlorambucil plus obinutuzumab in first-line CLL” abbvie.com ↗
release “The approval is based on the pivotal Phase 3 GLOW study that demonstrated superior progression-free survival (PFS) in patients treated with I+V versus chlorambucil-obinutuzumab (Clb+O)” jnj.com ↗
release “the Phase 3 GLOW study (Abstract #93), whichshowed investigational, fixed-duration treatment with IMBRUVICA®+ venetoclax (I+V) reduced the risk of progression or death by 79 percent” jnj.com ↗
release “GLOW study showed that the fixed-duration combination regimen of VENCLYXTO and ibrutinib demonstrated a clinically meaningful improvement in PFS” abbvie.com ↗
Publications
- Kater 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.
- Niemann 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.
- Moreno 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Chlorambucil | Other / unclassified | 0.5 mg/kg | Oral |
| Subject | Ibrutinib | Small molecule | 420 mg | Oral |
| Comparator | Obinutuzumab | Monoclonal antibody | 1000 mg | Intravenous |
| Subject | Venetoclax | Small molecule | 400 mg | Oral |