Design and Goals of the Phase 3 GLOW Study for CLL

Carolyn Owen, MD, associate professor in the Division of Hematology & Hematological Malignancies, University of Calgary, and hematologist at the Tom Baker Cancer Center, discusses the phase 3 GLOW study (NCT03462719) which evaluated fixed-duration ibrutinib (Imbruvica) and venetoclax (Venclexta) in elderly or unfit patients with chronic lymphocytic leukemia (CLL).

The randomized, open-label, phase 3 study enrolled 211 patients with CLL or small lymphocytic lymphoma who were aged 65 years or older or 18-64 years with a cumulative illness rating scale score of greater than 6 or creatinine clearance of less than 70 mL/min had, had an ECOG performance status of less than or equal to 2, and measurable nodal disease.

In the frontline, this combination of ibrutinib and venetoclax elicited deep and prolonged undetectable minimal residual disease responses compared with the treatment combination of chlorambucil and obinutuzumab (Gazyva).

Transcription:

0:08 | As mentioned, this is a phase 3 randomized clinical trial which is very important because that's usually what leads to funding and that's the highest quality evidence. The comparator of chlorambucil obinutuzumab may not be the best for a lot of people because it wasn't a terribly popular treatment by the time this study was completed, but it was still an accepted standard of care at the time the study was started. Most people would question how this IV combination compares against venetoclax and obinutuzumab, which is a fixed duration novel agent-based therapy. But at the time, that wasn't routinely available in most places so I think you can argue that the selection of the chlorambucil obinutuzumab was a reasonable comparator.

0:52 | But because chlorambucil obinutuzumab was not a treatment we would give to the very fit, the inclusion criteria was goaled around patients who were not appropriate for intensive chemoimmunotherapy, either by age or by comorbidities. It excluded patients who had a known deletion 17P or TP53 mutation, because those patients are known to do poorly with chemoimmunotherapy.