Ublituximab in Combination With Ibrutinib Versus Ibrutinib Alone in Participants With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL)

ORR: Percentage of participants with best overall response of partial response(PR) and complete response(CR). CR criteria: No evidence of new disease; Absolute lymphocyte count(ALC)\<4x10\^9/liter(L); Regression of all target nodal masses to ≤1.5 centimeters(cm) in longest diameter(LD); Normal spleen,liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; Absolute neutrophil count(ANC)\>1.5x10\^9/L,platelets≥100x10\^9/L,hemoglobin (Hgb)≥110 gram per liter(g/L). PR criteria: No evidence of new disease; Response in 2 of following if abnormal at baseline: ALC\<4x10\^9/L or \>=50% decrease from baseline in sum of products(SPD) of target nodal lesions; splenomegaly; hepatomegaly;\>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; response in any 1:ANC\>1.5x10\^9/L,platelets\>100x10\^9/L,Hgb\>110g/L or \>=50% increase over baseline in any of these.

Time frame: Up to 62 months

Population: ITT Population included all randomized participants.

The CR rate was defined as the percentage of participants who achieved CR. CR criteria: No evidence of new disease; ALC \<4 x 10\^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC \>1.5 x 10\^9/L, platelets ≥100 x 10\^9/L, Hgb ≥110 g/L.

Time frame: Up to 62 months

Population: ITT Population included all randomized participants.

DOR:Interval from first documentation of CR/PR to first documentation of PD or death from any cause.CR:ALC\<4x10\^9/L;Regression to normal of target nodal masses,nodal non-target disease,and no detectable non-nodal,non-target disease;Normal spleen,liver size;Morphologically negative bone marrow,No lymphoid nodules;ANC\>1.5x10\^9/L,Platelets≥100x10\^9/L,Hgb≥110 g/L.PR:Response in 2 or more:ALC\<4x10\^9/L,\>=50% drop from baseline in ALC or SPD of target nodal lesions,Hepatosplenomegaly,\>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules;Response in 1 or more:ANC\>1.5x10\^9/L,Platelets\>100x10\^9/L,Hgb\>110 g/L or \>=50% increase over baseline in any.PD:Response in 1 or more:new nodes,Hepatosplenomegaly,unequivocal extra-nodal lesion;≥50% increase from nadir in SPD of target lesions or LD of node/extra-nodal mass or Splenic/Hepatic size,Unequivocal increase in non-target disease,More aggressive histology;Drop of \>50% in platelets/\>20g/L in Hgb from highest on-study count.

Time frame: From the first dose of study drug until the first documentation of PD or death whichever occurs first or up to 62 months

Population: Participants in the ITT Population (included all randomized participants) who achieved either CR or PR were analyzed.

MRD negativity rate was defined as the percentage of participants who were MRD negative post-baseline. If a participant was determined to be MRD negative by peripheral blood, a bone marrow aspirate was obtained to assess MRD in the bone marrow.

Time frame: Up to 62 months

Population: ITT Population included all randomized participants.

An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related.

Time frame: From the first dose up to 30 days after the last dose of study drug (up to 57.3 months)

Population: Safety Population included all participants who received at least one dose of study medication (ublituximab + ibrutinib or ibrutinib alone).

PFS was defined as the time from the date of randomization until the date of first documentation of definitive disease progression (PD) or date of death from any cause, whichever occurs first. PD requires at least one of the following: New nodes \>1.5 cm in the LD and \>1.0 in longest perpendicular diameter (LPD), new or recurrent hepatomegaly or splenomegaly, new or reappearance of an unequivocal extra-nodal lesion, ≥50% increase from the nadir in the sum of products of target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, \>50% decrease from the highest on-study platelet count, \>20 g/L decrease from the highest on-study Hgb.

Time frame: From the randomization until the first documentation of PD or death whichever occurs first or up to 62 months

Population: ITT Population included all randomized participants.

TTR was defined as the interval from the randomization to the first documentation of CR or PR. CR criteria: No evidence of new disease; ALC \<4 x 10\^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC \>1.5 x 10\^9/L, platelets ≥100 x 10\^9/L, Hgb ≥110 g/L. PR criteria: No evidence of new disease; Response in 2 of following when abnormal at baseline: ALC\<4 x 10\^9/L or \>=50% decrease from baseline in SPD of target nodal lesions; splenomegaly; hepatomegaly; \>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; and Response in 1 of the following: ANC\>1.5 x 10\^9/L, platelets\>100 x 10\^9/L, Hgb\>110 g/L or \>=50% increase over baseline in any of these.

Time frame: From the randomization up to 62 months

Population: Participants in the ITT Population (included all randomized participants) who achieved either CR or PR were analyzed.