Table 4.

Clinical studies of CIT use in CLL patients.

Clinical Study	Type of Study	Eligible Patients	Treatment	Endpoints	Conclusion	Ref.
FLAIR	Open label Randomized Phase III Controlled	Age between 18 and 75 years WHO performance status of 2 or lower Previously untreated CLL	Ibrutinib + rituximab (IR) vs. FCR	PFS	BR demonstrated a notable enhancement in PFS. It did not result in a significant improvement in OS.	[102]
CCL18	Multicenter Phase II Prospective Non-randomized	18 years old WHO performance status of 0 to 2 Life expectancy of at least 12 weeks Adequate renal and liver function	IR	Safety and efficacy of BR in previously untreated patients.	Apart from those with del(17p) who showed resistance to the treatment, the combination of BR is a safe and effective treatment for naïve CLL patients.	[103]
CCL10	Phase III Randomized Open label	Untreated fit patients with advanced CLL without del(17p)	FCR vs. BR	ORR	Smaller difference in median PFS between FCR and BR as well as no difference in OS.	[104]
ICLL-07-Filo	Phase II	≥18 years Binet stage C or Binet stage A and B with active disease. No prior treatment Absence of del(17p).	Obinutuzumab + ibrutinib followed by ibrutinib in patients achieving CR vs. FC-obinutuzumab in conjunction with ibrutinib.	PFS, OS, and minimal residual disease (MRD) in PB.	CIT with a set duration resulted in profound and lasting responses, leading to high survival rates. No distinctions were observed in the extent and persistence of MRD responses in PB based on the IGHV mutational status.	[105]