Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax Compared to Ublituximab in Combination With Umbralisib in Subjects With CLL (ULTRA-V)

Minimal Residual Disease (MRD) Negativity Rate

The MRD negativity rate was defined as the percentage of participants who achieved MRD negative status post-baseline, defined as a quantitative detection of less than one CLL/SLL cell in 10000 leukocytes by flow cytometry (MRD level, 10\^-4) in blood or bone marrow (BM). 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. Participants who did not have an MRD assessment at any post-baseline visits were considered non-responders and were included in the denominator when calculating MRD negativity rate.

Time frame: Up to 43.2 months

Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be 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: Up to 43.2 months

Phase 2: Time to Response (TTR) Per iwCLL 2018 Criteria

TTR was defined as the interval from enrollment to first documentation of CR, CRi, PR, or PR-L. TTR was analyzed via Kaplan-Meier method. CR=no evidence of new disease; ALC\<4x10\^9/L; regression of nodal masses to \<1.5cm LD; normal spleen ,liver size; no constitutional symptoms; cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age; ANC≥1.5x10\^9/L, platelet≥100x10\^9/L, Hb≥110g/L. CRi=CR criteria but with persistent anemia, thrombocytopenia, or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from BL in ALC (or decrease to\<4x10\^9/L) or SPD of target nodal lesions or CLL/SLL marrow infiltrate/B-lymphoid; no target, splenic, liver, or non-target disease with worsening that meets criteria for definitive PD; platelet\>100x10\^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to\<4x10\^9/L.

Time frame: Up to 43.2 months

Phase 2: Duration of Response (DOR) Per iwCLL 2018 Criteria

DOR=interval from 1st documentation of CR,CRi,PR or PR-L to earlier of 1st documentation of definitive PD or death from any cause.CR=no evidence of new disease;ALC\<4x10\^9/L;regression of nodal masses to\<1.5cm LD;normal spleen,liver size;no constitutional symptoms;cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age;ANC≥1.5x10\^9/L,platelet≥100x10\^9/L,Hb≥110g/L.CRi=CR criteria but with persistent anemia,thrombocytopenia,neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from BL in ALC(or decrease to\<4x10\^9/L) or SPD of target nodal lesions or CLL/SLL marrow infiltrate/Blymphoid;no target,splenic,liver,or non-target disease with worsening that meets criteria for definitive PD;platelet\>100x10\^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria;not≥50% decrease from BL in ALC/decrease to\<4x10\^9/L.PD=evidence of new disease per protocol-specififed criteria.

Time frame: Up to 43.2 months

Phase 3: CR Rate as Assessed by an Independent Review Committee (IRC) Per iwCLL 2018 Criteria

CR rate=percent of participants who achieved CR or CRi. CR=no evidence of new disease; ALC\<4x10\^9/L; regression of nodal masses to \<1.5 cm LD; normal spleen, liver size; no constitutional symptoms; cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age; ANC ≥1.5x10\^9/L, platelet ≥100x10\^9/L, Hb ≥110g/L. CRi=CR criteria but with persistent anemia,thrombocytopenia,or neutropenia/hypocellular BM related to prior/ongoing drug toxicity. CR assessment was subject to independent confirmation by the IRC in participants enrolled to the Phase 3 stage of the study.

Time frame: Up to 43.2 months

Phase 3: ORR as Assessed by IRC Per iwCLL 2018 Criteria

ORR=percent of participants who achieve CR, CRi, PR or PR-L.CR=no evidence of new disease; ALC\<4x10\^9/L; regression of nodal masses to\<1.5cm LD; normal spleen and liver size; no constitutional symptoms; cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age; ANC≥1.5x10\^9/L, platelet≥100x10\^9/L, Hb≥110g/L. CRi=CR criteria but with persistent anemia, thrombocytopenia, or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from baseline (BL) in ALC (or decrease to\<4x10\^9/L) or SPD of target nodal lesions or CLL/SLL marrow infiltrate/B-lymphoid; no target, splenic, liver, or non-target disease with worsening that meets criteria for definitive PD; platelet\>100x10\^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to\<4x10\^9/L.

Time frame: Up to 43.2 months

Phase 3: Overall Survival (OS)

Overall Survival (OS) was defined as the interval from randomization to death from any cause. OS data was censored at the last documented date that the participant was confirmed alive for participants who withdrew consent or were lost to follow-up prior to the end of the study, and for participants whose vital status in the study could not be determined.

Time frame: Up to 43.2 months