Trial Outcomes & Findings for A Phase II, Open Label, Single Arm, Multicenter Study of Chlorambucil in Japanese Previously Untreated Patients With Chronic Lymphocytic Leukemia (NCT NCT01808326)

Last Updated: 2015-06-22

Results Overview

According to the criteria based on the 2008 revision of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) of the National Cancer Institute-Sponsored Working Group Guidelines (NCI-WG), participants with complete remission (CR), nodular partial remission (nPR), complete remission-incomplete (CRi) and partial remission (PR) were classified as responders, while stable disease (SD) and progressive disease (PD) were classified as non-responders. Participants with unknown or missing responses were considered as non-responders. Assessment was completed by the Investigator, Independent Review Committee (IRC), and IRC with Computed Tomography (CT).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

From the start of treatment until disease progression or death (up to Week 61.1)

Results posted on

2015-06-22

Participant Flow

This study consisted of three phases: Screening Phase (within 6 weeks prior to Day 1), Treatment Phase (up to 48 weeks) and Follow-up Phase (up to 24 Weeks).

Participants with Chronic Lymphocytic Leukemia (CLL) were enrolled after blood sampling, physical examination, and Computed Tomography (CT) scan. The physical examination was performed \<=14 days prior to Visit 2, CT scan performed within 6 weeks and the bone marrow examination within 6 weeks prior to Day 1.

Participant milestones

Participant milestones
Measure	Chlorambucil 10 mg/m^2 Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Overall Study STARTED	5
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase II, Open Label, Single Arm, Multicenter Study of Chlorambucil in Japanese Previously Untreated Patients With Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Age, Continuous	73.2 Years STANDARD_DEVIATION 7.63 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the start of treatment until disease progression or death (up to Week 61.1)

Population: All Subjects Population: all participants who received at least one dose of investigational product.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Number of Participants With a Best Response of Either Complete Remission (CR), Nodular Partial Remission (nPR), Complete Remission-incomplete (CRi) or Partial Remission (PR), as Assessed by the Investigator, IRC and IRC With CT IRC with CT Assessed	3 Participants
Number of Participants With a Best Response of Either Complete Remission (CR), Nodular Partial Remission (nPR), Complete Remission-incomplete (CRi) or Partial Remission (PR), as Assessed by the Investigator, IRC and IRC With CT IRC Assessed	5 Participants
Number of Participants With a Best Response of Either Complete Remission (CR), Nodular Partial Remission (nPR), Complete Remission-incomplete (CRi) or Partial Remission (PR), as Assessed by the Investigator, IRC and IRC With CT Investigator-Assessed	5 Participants

SECONDARY outcome

Timeframe: From the start of treatment until disease progression or death (up to Week 61.1)

Population: All Subjects Population

OR is defined as the number of participants achieving either a confirmed CR or PR. Assessment was completed by the Investigator, IRC, and IRC with CT. CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) \> 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils \>1500 per microliter (µL), platelets (PL) \>100,000/µL, hemoglobin (Hb) \>11 grams/deciliter (g/dL), lymphocytes (LC) \<4000/µL, bone marrow (BM) sample must be normocellular for age, \<30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: \>=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL \>100,000/µL or 50% improvement over Baseline (BL), Hb \>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT Investigator-Assessed, CR	0 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT Investigator-Assessed, CRi	0 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT Investigator-Assessed, nPR	0 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT Investigator-Assessed, PR	5 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT Investigator-Assessed, Responders	5 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC Assessed, CR	0 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC Assessed, CRi	0 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC Assessed, nPR	0 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC Assessed, PR	5 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC Assessed, Responders	5 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC with CT Assessed, CR	0 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC with CT Assessed, CRi	0 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC with CT Assessed, nPR	0 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC with CT Assessed, PR	3 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT IRC with CT Assessed, Responders	3 Participants

SECONDARY outcome

Timeframe: From the start of treatment until disease progression or death (up to Week 61.1)

Population: All Subjects Population

Progression-free survival (PFS) is defined as the time from the start of treatment of investigational product until the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd lymph nodes (\>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event or death occurred after extensive lost-to-follow-up time or if new anti-cancer therapy was started were censored at the date of the last visit with adequate assessment.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Progression Free Survival (PFS), as Assessed by the Investigator and the IRC IRC Assessed	NA Weeks No PFS could be determined because no progression or death was observed in the participants up to follow up 28 weeks after the final day of the last treatment, and all participants were censored for analysis.
Progression Free Survival (PFS), as Assessed by the Investigator and the IRC Investigator Assessed	NA Weeks No PFS could be determined because no progression or death was observed in the participants up to follow up 28 weeks after the final day of the last treatment, and all participants were censored for analysis.

SECONDARY outcome

Timeframe: From the start of treatment until death (up to Week 61.1)

Population: All Subjects Population

Overall survival is defined as time from the start of treatment until death due to any cause. Participants who had not died were censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Overall Survival (OS)	NA Weeks All 5 participants were alive at the time of the last follow-up and thus were censored for the analysis

SECONDARY outcome

Timeframe: From the start of treatment until the first response (CR/PR) (up to Week 61.1)

Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Time to response is defined as time from the start of treatment until the first response (CR/PR). Time to Response analyses was restricted to the subgroup of the population who experienced an overall response (CR/ nPR/CRi/PR) during the study. CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) \> 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils \>1500 per microliter (µL), platelets (PL) \>100,000/µL, hemoglobin (Hb) \>11 grams/deciliter (g/dL), lymphocytes (LC) \<4000/µL, bone marrow (BM) sample must be normocellular for age, \<30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: \>=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL \>100,000/µL or 50% improvement over Baseline (BL), Hb \>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Time to Response, as Assessed by the IRC	4.1 Weeks Interval 4.1 to 25.0

SECONDARY outcome

Timeframe: From the initial response (CR/PR) until disease progression or death (up to Week 61.1)

Population: All Subjects Population

Duration of response is defined as the time from the initial response (CR or PR) until progression or death. CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) \> 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils \>1500 per microliter (µL), platelets (PL) \>100,000/µL, hemoglobin (Hb) \>11 grams/deciliter (g/dL), lymphocytes (LC) \<4000/µL, bone marrow (BM) sample must be normocellular for age, \<30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: \>=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL \>100,000/µL or 50% improvement over Baseline (BL), Hb \>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Duration of Response, as Assessed by the IRC	NA Weeks The duration of response could not be assessed because no progression was observed in any of 5 participants up to Week 72

SECONDARY outcome

Timeframe: From the start of treatment until the first administration of the next CLL treatment (up to Week 61.1)

Time to next CLL therapy is defined as the time from start of treatment until the first administration of the next CLL treatment other than chlorambucil administrations scheduled in this study. Time to next CLL therapy was restricted to the subgroup of the population who receive a next CLL therapy after experiencing disease progression.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy	NA Weeks No data were available because no participants received the next CLL therapy

SECONDARY outcome

Timeframe: Baseline, Cycle (C) 2-Day (D) 29, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9-D225, FU 1- PDFU 1, FU 85-PDFU 85, and FU 169-PDFU 169

ECOG PS is a scale to assess disease progression, extent to which disease affects the daily living abilities and determines appropriate treatment and prognosis. It is scored on a scale of 0 to 5 as, 0 (fully active), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2 (ambulatory and capable of all self cares but unable to carry out any work activities, Up and about \> 50% of waking hours), 3 (capable of only limited self cares, confined to bed or chair \> 50% of waking hours), 4 (completely disabled, cannot carry on any self cares, totally confined to bed or chair), 5 (death). Improvement is defined as decrease from baseline by at least one step on the ECOG performance status scale (yes/no). Baseline was last pre-dose assessment performed on Cycle 1 Day 1(C1 D1). When C1 D1 was missing, the last assessment performed prior to pre-dose C1 D1 was used. It was performed on Day 1 of each cycle and follow-up (FU).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 8-Day 197, No Change, n=1	1 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) FU 169-PDFU 169, No Change, n=5	4 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 2-Day 29, Improved, n=5	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 2-Day 29, No Change, n=5	5 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 2-Day 29, Deteriorated, n=5	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 3-Day 57, Improved, n=4	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 3-Day 57, No Change, n=4	4 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 3-Day 57, Deteriorated, n=4	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 4-Day 85, Improved, n=4	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 4-Day 85, No Change, n=4	4 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 4-Day 85, Deteriorated, n=4	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 5-Day 113, Improved, n=4	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 5-Day 113, No Change, n=4	4 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 5-Day 113, Deteriorated, n=4	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 6-Day 141, Improved, n=4	1 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 6-Day 141, No Change, n=4	3 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 6-Day 141, Deteriorated, n=4	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 7-Day 169, Improved, n=1	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 7-Day 169, No Change, n=1	1 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 7-Day 169, Deteriorated, n=1	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 8-Day 197, Improved, n=1	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 8-Day 197, Deteriorated, n=1	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 9-Day 225, Improved, n=1	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 9-Day225, No Change, n=1	1 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Cycle 9-Day 225, Deteriorated, n=1	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) FU 1-PDFU 1, Improved, n=5	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) FU 1-PDFU 1, No Change, n=5	5 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) FU 1-PDFU 1, Deteriorated, n=5	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) FU 85-PDFU 85, Improved, n=5	1 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) FU 85-PDFU 85, No Change, n=5	4 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) FU 85-PDFU 85, Deteriorated, n=5	0 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) FU 169-PDFU 169, Improved, n=5	1 Participants
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) FU 169-PDFU 169, Deteriorated, n=5	0 Participants

SECONDARY outcome

Timeframe: Baseline, C2-D29, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9-D225, FU 1-PDFU 1, FU 85-PDFU 85, and FU 169-PDFU 169

The number of participants with no B-symptoms (no night sweat, no weight loss, no fever and no extreme fatigue) and the number of participants with at least one of the B-symptoms are summarized by assessment time. The presence of the B-symptoms was assessed at Baseline, Day 1 of each treatment cycle and follow-up (FU). Baseline was the last pre-dose assessment performed at C1 D1.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Baseline, With no B-symptom, n=5	3 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Baseline, With at least one B-symptom, n=5	2 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 2-Day 29, With no B-symptom , n=5	4 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 2-Day 29, With at least one B-symptom, n=5	1 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 3-Day 57, With no B-symptom, n=4	4 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 3-Day 57, With at least one B-symptom, n=4	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 4-Day 85, With no B-symptom, n=4	4 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 4-Day 85, With at least one B-symptom, n=4	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 5-Day 113, With no B-symptom, n=4	4 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 5-Day 113, With at least one B-symptom, n=4	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 9-Day 225,With at least one B-symptom, n=1	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time FU 1-PDFU 1,With no B-symptom, n=5	5 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time FU 1-PDFU 1,With at least one B-symptom, n=5	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time FU 85-PDFU 85,With no B-symptom ,n=5	5 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time FU 85-PDFU 85,With at least one B-symptom, n=5	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time FU 169-PDFU 169, With no B-symptom, n=5	5 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time FU 169-PDFU 169, With at least one B-symptom, n=5	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 6-Day 141, With no B-symptom, n=4	4 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 6-Day 141, With at least one B-symptom, n=4	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 7-Day 169, With no B-symptom, n=1	1 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 7-Day 169, With at least one B-symptom, n=1	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 8-Day 197, With no B-symptom, n=1	1 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 8-Day 197, With at least one B-symptom, n=1	0 Participants
Number of Participants With no B-symptoms and With at Least One B-symptom Over Time Cycle 9-Day 225, With no B-symptom, n=1	1 Participants

SECONDARY outcome

Timeframe: From the start of treatment up to Week 61.1

Population: All Subjects Population

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, is a congenital anomaly/birth defect or is associated with protocol specified liver injury and impaired liver function or is any protocol specific AEs.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Number of Participants With Any Adverse Events (AE) or Serious Adverse Events (SAE) Any AE	5 Participants
Number of Participants With Any Adverse Events (AE) or Serious Adverse Events (SAE) Any SAE	1 Participants

SECONDARY outcome

Timeframe: From the start of treatment up to Week 61.1

Population: All Subjects Population

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. Non-hematologic AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE V4.03): Grade 0, none; Grade 1, mild; Grade 2, moderate; Grade 3, severe or medically significant; Grade 4, life-threatening consequences; Grade 5, death related to AE

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Number of Participants With Adverse Events by the Indicated Maximum Toxicity Grade Grade 1	0 Participants
Number of Participants With Adverse Events by the Indicated Maximum Toxicity Grade Grade 2	2 Participants
Number of Participants With Adverse Events by the Indicated Maximum Toxicity Grade Grade 3	3 Participants
Number of Participants With Adverse Events by the Indicated Maximum Toxicity Grade Grade 4	0 Participants
Number of Participants With Adverse Events by the Indicated Maximum Toxicity Grade Grade 5	0 Participants

SECONDARY outcome

Timeframe: From the start of treatment up to Week 61.1

Population: All Subjects Population

Number of participants with a Grade 3 or Grade 4 adverse event of infection or myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Number of Participants With at Least One Grade 3/Grade 4 Adverse Event of Infection or Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia) Infection, Grade 3	0 Participants
Number of Participants With at Least One Grade 3/Grade 4 Adverse Event of Infection or Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia) Infection, Grade 4	0 Participants
Number of Participants With at Least One Grade 3/Grade 4 Adverse Event of Infection or Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia) Myelosuppression, Grade 3	3 Participants
Number of Participants With at Least One Grade 3/Grade 4 Adverse Event of Infection or Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia) Myelosuppression, Grade 4	0 Participants

SECONDARY outcome

Timeframe: Baseline, FU 1-PDFU 1, FU 85-PDFU 85, and FU 169-PDFU 169

Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants.Peripheral samples were collected for the analysis of IgA, IgG, and IgM at Baseline and 28 days after Day 1 of the last treatment cycle (FU 1-PDFU 1) for all participants, and 168 days after day of FU 1-PDFU 1 for participants with CR, PR, and SD. Baseline was the last pre-dose assessment performed on Cycle 1-Day 1. The the last assessment performed prior to pre-dose Cycle 1-Day 1 was used if Cycle 1-Day 1 was missing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Change From Baseline in the Immunoglobulin(Ig) Antibodies IgA, IgG, and IgM IgA, FU 1-PDFU 1, n=5	-0.092 Grams per liter Standard Deviation 0.2792
Change From Baseline in the Immunoglobulin(Ig) Antibodies IgA, IgG, and IgM IgA, FU 169-PDFU 169, n=4	-0.053 Grams per liter Standard Deviation 0.2185
Change From Baseline in the Immunoglobulin(Ig) Antibodies IgA, IgG, and IgM IgG, FU 1-PDFU 1, n=5	-0.446 Grams per liter Standard Deviation 1.2509
Change From Baseline in the Immunoglobulin(Ig) Antibodies IgA, IgG, and IgM IgG, FU 169-PDFU 169, n=4	0.340 Grams per liter Standard Deviation 0.8328
Change From Baseline in the Immunoglobulin(Ig) Antibodies IgA, IgG, and IgM IgM, FU 1-PDFU 1, n=4	-0.068 Grams per liter Standard Deviation 0.3402
Change From Baseline in the Immunoglobulin(Ig) Antibodies IgA, IgG, and IgM IgM, FU 169-PDFU 169, n=3	0.113 Grams per liter Standard Deviation 0.1185

SECONDARY outcome

Timeframe: From the start of treatment up to Week 61.1

Population: All Subjects Population

MRD refers to the small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed CR and in whom bone marrow test was performed. A bone marrow sample was examined by flow cytometry (Cluster of differentiation \[CD\]5, CD19, CD20, and CD23). MRD positive is defined as more than one CLL cell per 10000 leukocytes.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Number of Participants With Positive Minimal Residual Disease (MRD)	1 Participants

SECONDARY outcome

Timeframe: Baseline (Cycle 1 Day 1)

Population: All Subjects Population

Blood samples were collected at the Baseline (Day 1 of Cycle 1) visit for prognostic biomarker Beta 2 microglobulin measurements.

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Expression of Beta 2 Microglobulin	263.3906 Nanomoles per Liter Standard Deviation 25.82599

SECONDARY outcome

Timeframe: Baseline, Cycle 1-Day 1, and Cycle 4-Day 85

Peripheral samples were collected for the analysis of complement CH50 at Baseline (Day 1 of Cycle 1) and after completion of Cycle 4 (Day 85).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Expression of Complement CH50 Cycle 1-Day 1, n=4	45.48 Kilounit /Liter Standard Deviation 3.037
Expression of Complement CH50 Cycle 4-Day 85, n=4	40.08 Kilounit /Liter Standard Deviation 10.942

SECONDARY outcome

Timeframe: Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 1

Population: PK Population: all participants who received at least one dose of investigational product and for whom PK data was collected. Only those participants with non-missing values available at the specified time points were analyzed (represented by n=X in the category titles).

Blood samples for pharmacokinetic (PK) analysis of chlorambucil were collected on Day 1 and Day 4 in Cycle 1, and on Day 1 in Cycle 3. In each sampling, blood samples (2 milliliter \[mL\]/sample) were collected at pre-dose, and 15 minute (min), 30 min, 1 hour (hr), 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Maximum serum concentration (Cmax), minimum serum concentration (Cmin) were determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Chlorambucil Cmax, Cycle 1-Day 1, n=5	746.846 Nanograms per milliliter Interval 499.393 to 1116.913
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Chlorambucil Cmax, Cycle 1-Day 4, n=4	884.046 Nanograms per milliliter Interval 679.823 to 1149.621
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Chlorambucil Cmax, Cycle 3-Day 57, n=4	691.960 Nanograms per milliliter Interval 553.342 to 865.303
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Chlorambucil Cmin, Cycle 1-Day 4, n=5	NA Nanograms per milliliter The Cmin value was non quantifiable (NQ) for all time points.
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Chlorambucil Cmin, Cycle 3-Day 57, n=4	NA Nanograms per milliliter The Cmin value was non quantifiable (NQ) for all time points.

SECONDARY outcome

Timeframe: Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Population.

Blood samples for PK analysis of chlorambucil were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. AUC from time zero up to a definite time t (AUC\[0-t\]), AUC from time zero up to infinity (AUC\[0-inf\]), AUC from time zero up to 6 hours post dose (AUC\[0-6\]), AUC from time zero up to 24 hours post dose (AUC\[0-24\]) were determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-24), Cycle 3-Day 57, n=4	1334.2607 Hour*nanogram/ milliliter/milligram Interval 990.8919 to 1796.6153
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-t), Cycle 1-Day 1, n=5	1207.8510 Hour*nanogram/ milliliter/milligram Interval 890.7718 to 1637.7978
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-t),Cycle 1-Day 4, n=4	1391.5506 Hour*nanogram/ milliliter/milligram Interval 1078.6087 to 1795.2878
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-t), Cycle 3-Day 57, n=4	1274.2668 Hour*nanogram/ milliliter/milligram Interval 1043.5229 to 1556.0327
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-inf), Cycle 1-Day 1, n=5	1230.8109 Hour*nanogram/ milliliter/milligram Interval 910.1764 to 1664.3978
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-inf), Cycle 1-Day 4, n=4	1408.1764 Hour*nanogram/ milliliter/milligram Interval 1094.5401 to 1811.6841
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-inf), Cycle 3-Day 57, n=4	1354.2258 Hour*nanogram/ milliliter/milligram Interval 960.1552 to 1910.0323
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-24), Cycle 1-Day 1, n=5	1230.6335 Hour*nanogram/ milliliter/milligram Interval 910.013 to 1664.2168
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-24), Cycle 1-Day 4, n=4	1408.1363 Hour*nanogram/ milliliter/milligram Interval 1094.504 to 1811.6406
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-6), Cycle 1-Day 1, n=5	1183.4581 Hour*nanogram/ milliliter/milligram Interval 869.4781 to 1610.8205
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-6), Cycle 1-Day 4, n=4	1375.8404 Hour*nanogram/ milliliter/milligram Interval 1081.1272 to 1750.8917
Area Under the Serum Concentration-time (AUC) for Chlorambucil AUC(0-6), Cycle 3-Day 57, n=4	1246.9176 Hour*nanogram/ milliliter/milligram Interval 1056.4256 to 1471.7587

SECONDARY outcome

Timeframe: Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Blood samples for pharmacokinetic (PK) analysis of chlorambucil were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Elimination half-life (t1/2) was determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Elimination Half-life (t1/2) for Chlorambucil t1/2, Cycle 1-Day 1 , n=5	1.3488 Hour Interval 1.009 to 1.803
Elimination Half-life (t1/2) for Chlorambucil t1/2, Cycle 1-Day 4, n=5	1.3211 Hour Interval 0.9035 to 1.9316
Elimination Half-life (t1/2) for Chlorambucil t1/2, Cycle 3-Day 57, n=4	1.6979 Hour Interval 0.4245 to 6.7918

SECONDARY outcome

Timeframe: Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Blood samples for pharmacokinetic (PK) analysis of chlorambucil were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Time of maximum serum concentration (tmax) was determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Time of Maximum Serum Concentration (Tmax) for Chlorambucil tmax, Cycle 1-Day 1, n=5	1.000 Hour Interval 0.95 to 1.5
Time of Maximum Serum Concentration (Tmax) for Chlorambucil tmax, Cycle 1-Day 4, n=4	0.725 Hour Interval 0.48 to 1.5
Time of Maximum Serum Concentration (Tmax) for Chlorambucil tmax, Cycle 3-Day 57, n=4	0.975 Hour Interval 0.5 to 1.48

SECONDARY outcome

Timeframe: Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 1

Blood samples for pharmacokinetic (PK) analysis of chlorambucil and its metabolite phenyl acetic acid mustard were collected on Day 1 and Day 4 in Cycle 1, and on Day 1 in Cycle 3. In each sampling, blood samples (2 milliliter \[mL\]/sample) were collected at pre-dose, and 15 minute (min), 30 min, 1 hour (hr), 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Maximum serum concentration (Cmax), minimum serum concentration (Cmin) were determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Phenyl Acetic Acid Mustard Cmin, Cycle 3-Day 57, n=4	NA Nanograms per milliliter The Cmin value was non quantifiable (NQ) for all time points
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Phenyl Acetic Acid Mustard Cmax, Cycle 1-Day 1, n=5	502.942 Nanograms per milliliter Interval 418.135 to 604.949
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Phenyl Acetic Acid Mustard Cmax, Cycle 1-Day 4, n=4	516.310 Nanograms per milliliter Interval 406.414 to 655.923
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Phenyl Acetic Acid Mustard Cmax, Cycle 3-Day 57, n=4	417.660 Nanograms per milliliter Interval 345.801 to 504.451
Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Phenyl Acetic Acid Mustard Cmin, Cycle 1-Day 4, n=5	NA Nanograms per milliliter The Cmin value was non quantifiable (NQ) for all time points

SECONDARY outcome

Timeframe: Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Blood samples for PK analysis of chlorambucil and its metabolite phenyl acetic acid mustard were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. AUC from time zero up to a definite time t (AUC\[0-t\]), AUC from time zero up to infinity (AUC\[0-inf\]), AUC from time zero up to 6 hours post dose (AUC\[0-6\]), AUC from time zero up to 24 hours post dose (AUC\[0-24\]) were determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-t), Cycle 1-Day 1, n=5	1890.7202 Hour*nanogram/ milliliter/milligram Interval 1657.6433 to 2156.5694
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-t),Cycle 1-Day 4, n=4	1902.4232 Hour*nanogram/ milliliter/milligram Interval 1474.2957 to 2454.8766
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-t), Cycle 3-Day 57, n=4	1839.8498 Hour*nanogram/ milliliter/milligram Interval 1375.6347 to 2460.7168
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-inf), Cycle 1-Day 1, n=5	2015.0708 Hour*nanogram/ milliliter/milligram Interval 1783.4844 to 2276.7288
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-inf), Cycle 1-Day 4, n=4	2011.2434 Hour*nanogram/ milliliter/milligram Interval 1521.8953 to 2657.9357
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-inf), Cycle 3-Day 57, n=4	2012.4576 Hour*nanogram/ milliliter/milligram Interval 1422.5732 to 2846.9435
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-24), Cycle 1-Day 1, n=5	2013.1533 Hour*nanogram/ milliliter/milligram Interval 1781.2371 to 2275.2649
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-24), Cycle 1-Day 4, n=4	2008.6155 Hour*nanogram/ milliliter/milligram Interval 1521.3369 to 2651.9676
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-24), Cycle 3-Day 57, n=4	2007.1545 Hour*nanogram/ milliliter/milligram Interval 1422.7652 to 2831.5771
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-6), Cycle 1-Day 1, n=5	1568.5579 Hour*nanogram/ milliliter/milligram Interval 1339.5928 to 1836.658
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-6), Cycle 1-Day 4, n=4	1647.7794 Hour*nanogram/ milliliter/milligram Interval 1332.9712 to 2036.9359
Area Under the Serum Concentration-time (AUC) for Phenyl Acetic Acid Mustard AUC(0-6), Cycle 3-Day 57, n=4	1519.3633 Hour*nanogram/ milliliter/milligram Interval 1215.2713 to 1899.5468

SECONDARY outcome

Timeframe: Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Blood samples for pharmacokinetic (PK) analysis of chlorambucil and its metabolite phenyl acetic acid mustard were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Elimination half-life (t1/2) was determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Elimination Half-life (t1/2) for Phenyl Acetic Acid Mustard t1/2, Cycle 1-Day 1 , n=5	2.0929 Hour Interval 1.7061 to 2.5674
Elimination Half-life (t1/2) for Phenyl Acetic Acid Mustard t1/2, Cycle 1-Day 4, n=5	2.1846 Hour Interval 1.7179 to 2.7782
Elimination Half-life (t1/2) for Phenyl Acetic Acid Mustard t1/2, Cycle 3-Day 57, n=4	2.3495 Hour Interval 1.4906 to 3.7031

SECONDARY outcome

Timeframe: Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Blood samples for pharmacokinetic (PK) analysis of chlorambucil and its metabolite phenyl acetic acid mustard were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Time of maximum serum concentration (tmax) was determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Outcome measures

Outcome measures
Measure	Chlorambucil 10 mg/m^2 n=5 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Time of Maximum Serum Concentration (Tmax) for Phenyl Acetic Acid Mustard tmax, Cycle 1-Day 1, n=5	1.970 Hour Interval 1.5 to 2.0
Time of Maximum Serum Concentration (Tmax) for Phenyl Acetic Acid Mustard tmax, Cycle 1-Day 4, n=4	1.490 Hour Interval 1.47 to 2.0
Time of Maximum Serum Concentration (Tmax) for Phenyl Acetic Acid Mustard tmax, Cycle 3-Day 57, n=4	1.730 Hour Interval 1.47 to 2.0

Adverse Events

Chlorambucil 10 mg/m^2

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Chlorambucil 10 mg/m^2 n=5 participants at risk Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Infections and infestations Herpes zoster	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.

Other adverse events

Other adverse events
Measure	Chlorambucil 10 mg/m^2 n=5 participants at risk Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued
Blood and lymphatic system disorders Thrombocytopenia	100.0% 5/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Blood and lymphatic system disorders Neutropenia	80.0% 4/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Blood and lymphatic system disorders Anaemia	40.0% 2/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Investigations White blood cell count decreased	80.0% 4/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Investigations Aspartate aminotransferase increased	40.0% 2/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Investigations Blood lactate dehydrogenase increased	40.0% 2/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Investigations Lymphocyte count decreased	40.0% 2/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Investigations Alanine aminotransferase increased	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Investigations Blood alkaline phosphatase increased	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Investigations Haemoglobin decreased	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Investigations Neutrophil count decreased	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Nausea	40.0% 2/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Abdominal discomfort	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Abdominal pain upper	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Gastritis	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Skin and subcutaneous tissue disorders Pruritus	40.0% 2/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Skin and subcutaneous tissue disorders Rash maculo-papular	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
General disorders Fatigue	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
General disorders Malaise	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Infections and infestations Nasopharyngitis	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Infections and infestations Pharyngitis	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Immune system disorders Hypersensitivity	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	20.0% 1/5 • On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow-up contact (up to Week 61.1. On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.

Additional Information

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GlaxoSmithKline

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Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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