A Phase 3 Randomise study to Assess the Efficacy and Safety of Ublituximab in Combination with TGR-1202 Compared to Obinutuzumab in Combination with Chlorambucil in Patients with Chronic Lymphocytic Leukemia (CLL) (A Chronic lymphocytic leukemia (CLL) is a type of cancer that starts from cells that become certain white blood cells (called lymphocytes) in the bone marrow. The cancer (leukemia) cells start in the bone marrow but then go into the blood)

INTERVENTION: Product Name: Ublituximab Product Code: TG‐1101 Pharmaceutical Form: Solution for injection INN or Proposed INN: Ublituximab Current Sponsor code: TG‐1101 Other descriptive name: IgG1 immunoglobulins Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 10‐ Product Name: TGR‐1202 Product Code: TGR‐1202 Pharmaceutical Form: Tablet INN or Proposed INN: TGR‐1202 Current Sponsor code: TGR‐1202 Other descriptive name: (S)‐2‐(1‐(4‐amino‐3‐(3‐fluoro‐4‐isopropoxyphenyl)‐1H‐pyrazolo [3, 4‐d] pyrimidin‐1‐yl)‐ethyl)‐6‐fluoro‐3‐(3‐fluorophenyl)‐4H‐chromen‐4‐one 4 methylbenzenesulfonate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Trade Name: Gazyvaro 1,000 mg concentrate for solution for infusion. Product Name: Gazyvaro 1,000 mg concentrate for solution for infusion. Product Code: Obinutuzumab Pharmaceutical Form: Solution for infusion INN or Proposed INN: Obinutuzumab CAS Number: 949142‐50‐1 Current Sponsor code: Obinutuzumab Other descriptive name: Obinutuzumab Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 25‐ Trade Name: Chlorambucil 2 mg tablets Product Name: Chlorambucil 2 mg tablets Product Code: Chlorambucil Pharmaceutical Form: Tablet INN or Proposed INN: Chlorambucil CAS Number: 305‐03‐3 Current Sponsor code: Chlorambucil Other descriptive name: Chlorambucil Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ CONDITION: Chronic Lymphocytic Leukemia ; MedDRA version: 19.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To establish that the combination of ublituximab + TGR‐1202 is superior to the combination of obinutuzumab + chlorambucil as measured by Progression‐Free Survival (PFS) in patients with CLL Primary end point(s): Progression‐free survival (PFS); PFS is defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause.; Definitive disease progression based on standard criteria (Hallek et al. 2008) and occurring for any reason (i.e., increasing lymphadenopathy, organomegaly or bone marrow involvement; decreasing platelet count, hemoglobin, or neutrophil count; or worsening of disease‐related symptoms) other than lymphocytosis.; ; Overall response rate (ORR); ORR is defined as sum of CR and PR rates.; ; Complete Response (CR) Rate; CR rate is defined as the proportion of patients who achieve a CR.; ; Minimal Residual Disease (MRD) Negativity Rate; MRD negativity rate is defined as the proportion of patients who are MRD negative.; ; Duration of response (DOR); DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause. Secondary Objective: To establish that the combination of ublituximab + TGR‐1202 provides clinical benefit over both ublituximab alone and TGR‐1202 alone; To evaluate and compare the combination of ublituximab + TGR‐1202 to the combination of obinutuzumab + chlorambucil with respect to overall response rate in patients with CLL Timepoint(s) of evaluation of this end point: Each primary end points will be evaluated every three months SECONDARY OUTCOME: Secondary end point(s): Efficacy Timepoint(s) of evaluation of this end point: Efficacy will be evaluated every three months INCLUSION CRITERIA: 1. B‐cell CLL (treatment naïve or previously treated) that warrants treatment consistent with accepted IWCLL criteria for initiation of therapy. Any of the following conditions constitute CLL that warrants treatment: a. Evidence of progressive marrow failure as manifested by the onset or worsening of anemia and/or thrombocytopenia, or b. Massive (i.e., lower edge of spleen = 6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or c. Massive (i.e., = 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy, or d. Progressive lymphocytosis in the absence of infection, with an increase in blood absolute lymphocyte count (ALC) >50% over a 2‐month period or lymphocyte doubling time of <6 months (as long as initial ALC was =30,000/L), or e. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, or f. Constitutional symptoms, defined as any one or mo