A PHASE II, MULTICENTER, RANDOMIZED, CONTROLLED, OPEN-LABEL STUDY OF THE SAFETY, EFFICACY AND PHARMACOKINETICS OF ABT-263 IN COMBINATION WITH DOSE-INTENSIVE RITUXIMAB, OR DOSE-INTENSIVE RITUXIMAB ALONE, IN PREVIOUSLY UNTREATED PATIENTS WITH B-CELL, CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

INTERVENTION: Product Code: ABT‐263 Pharmaceutical Form: Oral solution INN or Proposed INN: Navitoclax Current Sponsor code: ABT‐263 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 25‐ Trade Name: Mabthera Product Name: Mabthera Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: RITUXIMAB CAS Number: 174722‐31‐7 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 10‐ Product Code: ABT‐263 Pharmaceutical Form: Tablet INN or Proposed INN: Navitoclax Current Sponsor code: ABT‐263 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Product Code: ABT‐263 Pharmaceutical Form: Tablet INN or Proposed INN: Navitoclax Current Sponsor code: ABT‐263 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ CONDITION: B Cell Chronic Lymphocytic Leukemia ; MedDRA version: 14.0 Level: LLT Classification code 10008956 Term: Chronic lymphatic leukaemia System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To evaluate the efficacy of ABT‐263 when given according to two different regimens in combination with dose‐intense rituximab in previously untreated patients with B‐cell CLL, as measured by progression‐free survival (PFS) based on investigator assessments Primary end point(s): The primary efficacy endpoint is PFS, defined as the time from randomization to; the first occurrence of progression or relapse (as defined in Appendix E of the protocol) as assessed by the investigator or death on study. Secondary Objective: • To evaluate the efficacy of dose‐intense, rituximab monotherapy in previously; untreated patients with B‐cell CLL; • To evaluate the efficacy of ABT‐263 when given according to two different; regimens in combination with dose‐intense rituximab in previously untreated; patients with B‐cell CLL; • To compare the pharmacokinetics of ABT‐263 and rituximab when administered; alone to that when the two therapies are administered in combination; • To investigate the effects of rituximab on the pharmacokinetics of ABT‐263; and the effects of ABT‐263 on rituximab pharmacokinetics ; • To evaluate the efficacy of rituximab monotherapy either alone or when; administered with ABT‐263 according to two different regimens in previously; untreated patients with B‐cell CLL; • To evaluate the safety and tolerability of ABT‐263 when given according to; two different regimens in combination with dose‐intense rituximab in; previously untreated patients with B‐cell CLL Timepoint(s) of evaluation of this end point: Time Frame: From randomization to the first occurrence of progression, relapse, or death on study (approximately 40 months from First Patient In [FPI]) SECONDARY OUTCOME: Secondary end point(s): Overall response rate (ORR) [ Time Frame: Approximately 40 months from FPI ] ; Duration of response [ Time Frame: Approximately 40 months from FPI ] ; Complete response (CR) rate [ Time Frame: Approximately 40 months from FPI ] ; ORR as assessed by a blinded, independent review [ Time Frame: Approximately 40 months from FPI ] ; Duration of response as assessed by a blinded, independent review [ Time Frame: Approximately 40 months from FPI ] ; CR rate as assessed by a blinded, independent review [ Time Frame: Approximately 40 months from FPI ] INCLUSION CRITERIA: INCLUSION CRITERIA: Previously untreated, CD20‐positive B‐cell CLL ECOG performance status of 0 or 1 Life expectancy > 6 months Willingness and capability to be accessible for follow‐up until study termination or death ; Progression‐free survival as assessed by a blinded, independent review [ Time Frame: From randomization to the first occurrence of progression, relapse, or death on study (approximately 40 months from FPI) ] ; Overall survival (OS) [ Time Frame: From randomization until death due to any cause (approximately 4 years after Last Patient In) ] Timepoint(s) of evaluation of this end point: Approximately 40 months from FPI For patients of reproductive potential (both males and females), use of a reliable means of contraception Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 57 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 63