Table 5.

Ibrutinib clinical studies in patients with CLL or SLL.

Clinical Study	Type of Study	Eligible Patients	Treatment	Endpoints	Conclusion	Refs.
RESONATE-2	Phase III, randomized, open label, multicenter.	CLL and small SLL patients (naïve or previously treated) and ineligible for purine analog therapy.	Ibrutinib vs. chlorambucil as first-line treatment	PFS, ORR, safety.	Ibrutinib demonstrated an extended OS. The extended RESONATE-2 data illustrate the advantages of initiating treatment with ibrutinib, even for patients exhibiting high risk.	[113,114]
PCYC-1102	Phase Ib/II study.	Patients receiving single-agent ibrutinib in first-line or r/r CLL/SLL.	Ibrutinib	Frequency and severity of AE	Ibrutinib demonstrated prolonged responses and sustained tolerability in first-line r/r CLL/SLL. Individuals who had a history of ≥4 prior therapies and those with del(17p) exhibited a higher frequency of progression.	[115]
ILLUMINATE	Phase III, randomized, open label.	Untreated CLL/SLL patients. Aged ≥ 65 or <65 years. At least one of the following conditions: cumulative illness rating score > 6, creatinine clearance < 70 mL/min, del(17p), or TP53 mut.	Ibrutinib + obinutuzumab vs. chlorambucil + obinutuzumab as a first-line therapy	PFS	Ibrutinib + obinutuzumab for individuals with previously untreated CLL showed prolonged PFS compared to chlorambucil + Obinutuzumab.	[116]
E1912	Phase III, randomized.	CLL naïve patients aged 70 or less years.	Long-term efficacy ibrutinib + rituximab vs. FCR	PFS, OS	OS improvement in patients treated with ibrutinib + rituximab. This therapy provides better PFS compared to FCR in both IGHVm and IGHVum CLL patients.	[117]
ALLIANCE A041202	Phase III, randomized, open label.	Adults aged ≥ 65 years who had not received prior treatment for CLL.	BR vs. ibrutinib vs. ibrutinib + rituximab	PFS	Ibrutinib demonstrates superior PFS in older CLL patients compared to BR. However, the disparity in treatment duration complicates the comparison of AE.	[118,119]