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)

PFS: time between date of randomization and date of disease progression, as assessed by IRC, or date of death due to any cause, whichever occurs first, regardless of use of subsequent anti-cancer therapy prior to PD or death using iWCLL2008 criteria : New enlarged lymph nodes \>15 mm, new hepatomegaly or splenomegaly, or other organ infiltrates, bone lesion, ascites or pleural effusion due to CLL; \>=50% increase in longest diameter (LDi) from nadir in existing lymph node (LDi \>15 mm) or \>=50% increase from nadir in sum of diameters of multiple nodes (and at least 1 node with LDi \>15 mm); \>=50% increase from nadir in enlargement of liver/spleen; \>=50% increase from baseline in lymphocyte count (ALC; to \>=5\*10\^9/L); or \>=50% increase from nadir in ALC in \>=2 serial assessments if ALC is \>=30000\*10\^9/L and lymphocyte doubling time is rapid unless considered treatment-related lymphocytosis; new cytopenia attributable to CLL; transformation to more aggressive histology.

Time frame: Up to 2 years 10 months

Population: The intent-to-treat (ITT) analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.

Complete response rate is defined as the percentage of participants who achieved complete response or complete response with an incomplete marrow recovery (CRi) on or prior to initiation of subsequent anti-leukemic therapy per the IRC assessment. International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils \>1.5\*10\^9/liter (L), platelets \>100\*10\^9/L, Hgb \>11 gram per deciliter (g/dL), absolute lymphocyte count \<4000/microliter (mcL) and normocellular bone marrow with \<30% lymphocytes and no B lymphoid nodules; CRi- CR with incomplete recovery of bone marrow.

Time frame: Up to 2 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.

DOR is defined as the interval between the date of initial documentation of a response including partial response with lymphocytosis (PRL) and the date of first documented evidence of PD or death or date of censoring per the IRC assessment. iWCLL 2008 criteria for PD: New enlarged nodes \>1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; \>= 50% increase from nadir in existing lymph node or \>=50% increase from nadir in sum of product of diameters of multiple nodes; \>=50% increase from nadir in enlargement of liver or spleen; \>=50% increase from baseline in lymphocyte count (and to \>=5\*10\^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology.

Time frame: Up to 2 years 10 months

Population: Population analyzed included ITT amongst who were responders (PR or better).

MRD-negative rate is defined as the percentage of participants who achieved MRD-negative status (that is, less than \[\<\] 1 chronic lymphocytic leukemia (CLL) cell per 10,000 leukocytes or \<0.01 percentage \[%\]) in the bone marrow as assessed by next-generation sequencing (NGS). Participants with missing MRD data were considered MRD positive.

Time frame: Up to 2 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.

Number of participants with abnormal clinical laboratory findings (hematology and serum chemistry) were reported.

Time frame: Up to 4 years 10 months

Population: The safety analysis set is defined as all randomized participants who received at least one dose of any one of the four study drugs (ibrutinib, venetoclax, chlorambucil, or obinutuzumab).

An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Time frame: Up to 4 years 10 months

Population: The safety analysis set is defined as all randomized participants who received at least one dose of any one of the four study drugs (ibrutinib, venetoclax, chlorambucil, or obinutuzumab).

ORR: percentage of participants who achieved best overall response of either CR, CRi, nodular PR (nPR) and partial response (PR). iWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils \>1.5\*10\^9/liter (L), platelets \>100\*10\^9/L, Hgb \>11 g/dL and ALC \<4000/mcL, normocellular bone marrow with \<30% lymphocytes and no B lymphoid nodules; CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but bone marrow biopsy shows B-lymphoid nodules (reflecting residual disease); PR-2 of following when abnormal at baseline: \>=50% decrease in ALC, \>=50% decrease in sum of products of multiple nodes, \>=50% decrease in enlargement of spleen or liver; and 1 of following: neutrophils \>1.5\*10\^9/L, Platelets \>100\*10\^9/L and Hgb\>11 g/dL or \>=50% improvement over baseline in any of these; 50% reduction in bone marrow infiltrates or B lymphoid nodules; no new enlarged nodes or new hepatosplenomegaly.

Time frame: Up to 2 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. Participants with missing post-randomization data were considered non-responders.

OS is defined as the time from date of randomization to date of death from any cause.

Time frame: Up to 4 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Sustained hemoglobin improvement is defined as the percentage of participants who achieved an increase in hemoglobin levels from baseline by \>= 2 grams per deciliter (g/dL) and lasts for at least 56 days without blood transfusion or growth factors.

Time frame: Up to 2 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.

Sustained platelet improvement is defined as the percentage of participants who achieved an increase in platelet levels from baseline by \>= 50% and lasts for at least 56 days without blood transfusion or growth factors.

Time frame: Up to 2 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.

Plasma concentrations of ibrutinib and venetoclax were determined by validated liquid chromatography-tandem mass spectrometry.

Time frame: Ibrutinib: Pre-dose-Day 1 of Cycles 2, 3, 5 and 6 (each cycle is defined as 28 days), Venetoclax: Pre-dose-Day 1 of Cycles 5 and 6

Population: The pharmacokinetics (PK) analysis set is defined as all randomized participants in Treatment Arm A who received at least one dose of ibrutinib and/or venetoclax and had at least one valid blood sample drawn for PK analysis. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this endpoint. Here, n (number analyzed) is defined as number of participants analyzed for specified category.

Time-to-next treatment was measured from the date of randomization to the start date of any subsequent anti-leukemic therapy.

Time frame: Up to 2 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.

Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score). Time to Worsening is defined as time interval (months) from randomization to first observation of deterioration. Worsening is defined as a decrease \>= 3 points (on a 0-52 scale). Time to improvement is defined as the time interval (months) from randomization to the first observation of improvement. Improvement is defined as an increase \>=3 points (on a 0-52 scale).

Time frame: Up to 2 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.

Time to worsening= time interval (months) from randomization to first observation of deterioration. EQ-5D-5L consists of a 5-item descriptive system and the EuroQol visual analog scale (EQ-5D VAS). EQ-5D-VAS self-rating records respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Worsening is defined as a decrease of \>= 7 points (on a 0-100 scale). EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe participant's current health state. Responses for 5 dimensions are combined into a 5-digit number describing respondents health state that can be converted into a single index value or utility score (using the United Kingdom weights), ranging from -1 to 1, where lower scores indicate a worse health status. Worsening is defined as a decrease of \>=0.08 points (on a 0-1 scale).

Time frame: Up to 2 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.

Time to worsening= time interval from randomization to first observation of deterioration. EORTC QLQ-C30 includes 30 separate items: 5 functional scales (physical, role, emotional, cognitive, and social Functioning), 1 global health status (GHS) and QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each item, except GHS, is answered on 4-point scale (1=not at all to 4=very much) and GHS is measured on 1-7 scale: 1=very poor and 7=excellent. Scores derived using validated scoring algorithms as per EORTC QLQ-C30 Manual and linearly transformed in a range from 0-100. For functional and global QoL scales, higher scores=better level of functioning/QoL. For symptom-oriented scales, higher score=more severe symptoms. Worsening in functional and global health scores=decrease of \>=10 points (on 0-100 scale) and in symptom scores=increase of \>=10 points (on 0-100 scale).

Time frame: Up to 2 years 10 months

Population: The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.