Trial Outcomes & Findings for Ofatumumab Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia (NCT NCT00824265)

Last Updated: 2020-06-18

Results Overview

PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (progressive disease,PD) and the date of 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 (CLL).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

365 participants

Primary outcome timeframe

From randomization up to 5 years after last dose of study drug

Results posted on

2020-06-18

Participant Flow

Participants (par) were screened within 14 days prior to the start of study drug administration to determine eligibility.

Eligible par were stratified by Stage (Binet A vs. B vs. C) and number of prior therapies (1-2 vs. ≥3). Par in each stratum were then centrally randomized in a 1:1 ratio to recive intravenous (IV) fludarabine and cyclophosphamide in combination with ofatumumab or IV fludarabine and cyclophosphamide alone.

Participant milestones

Participant milestones
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Treatment Phase STARTED	183	182
Treatment Phase COMPLETED	119	102
Treatment Phase NOT COMPLETED	64	80
Follow-up Phase STARTED	172	160
Follow-up Phase COMPLETED	154	129
Follow-up Phase NOT COMPLETED	18	31
Survival Follow-up Phase STARTED	96	89
Survival Follow-up Phase COMPLETED	87	73
Survival Follow-up Phase NOT COMPLETED	9	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Treatment Phase Adverse Event,non-fatal	50	52
Treatment Phase Protocol Violation	1	0
Treatment Phase Lost to Follow-up	1	1
Treatment Phase Physician Decision	6	12
Treatment Phase Withdrawal by Subject	6	15
Follow-up Phase w/drew consent, no f/u, or MD choice	18	31
Survival Follow-up Phase w/drew consent, no f/u, or MD choice	9	16

Baseline Characteristics

Ofatumumab Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Total n=365 Participants Total of all reporting groups
Age, Continuous	61.4 Years STANDARD_DEVIATION 8.82 • n=5 Participants	61.6 Years STANDARD_DEVIATION 10.21 • n=7 Participants	61.5 Years STANDARD_DEVIATION 9.53 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	66 Participants n=7 Participants	145 Participants n=5 Participants
Sex: Female, Male Male	104 Participants n=5 Participants	116 Participants n=7 Participants	220 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	13 Participants n=5 Participants	16 Participants n=7 Participants	29 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	158 Participants n=5 Participants	153 Participants n=7 Participants	311 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization up to 5 years after last dose of study drug

Population: Intent-to-Treat (ITT) Population: all participants randomized and received study drug.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Progression-free Survival (PFS), as Assessed by the Independent Review Committee (IRC)	28.94 Months Interval 22.8 to 35.88	18.83 Months Interval 14.42 to 25.82	—	—

SECONDARY outcome

Timeframe: From randomization up to 5 years after last dose of study drug

Population: ITT Population.

Overall survival is defined as the time from randomization to death due to any cause. Each participant was followed at the time when the last IRC-assessed PFS events occurred. Participants who had not died were censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Survival (OS)	62.65 Months Interval 44.58 to Upper limit was not able to calculate due to an insufficient number of events (high censoring rate) and high follow-up time	46.23 Months Interval 37.72 to 56.57	—	—

SECONDARY outcome

Timeframe: From randomization up to 5 years after last dose of study drug

Population: ITT Population. Participants with unknown or missing responses were considered as non-responders. Only responders were included in the analysis.

Time to response is defined as the time from randomization to the first response. Complete Response/remission(CR) all the criteria at least 2 months after last treatment: no lymphadenopathy(Ly) \> 1.5 cm/ hepatomegaly/spleenomegaly/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. Incomplete bone marrow recovery(CRi): CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. Partial Remission/response(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. Nodular PR(nPR): persistent nodules BM.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=152 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=123 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Time to Response, as Assessed by the IRC	0.99 Months Interval 0.95 to 1.08	0.99 Months Interval 0.95 to 1.18	—	—

SECONDARY outcome

Timeframe: From time of initial response to disease progression or death, whichever came first (up to 5 years after the last dose of study drug)

Population: ITT Population. Par with unknown or missing responses were considered as non-responders, only responders were included in this analysis.

DOR is defined as the time from the initial response (CR, CRi, nPR, or PR) to 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.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=152 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=123 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Duration of Response (DOR), as Assessed by the IRC	29.63 Months Interval 25.03 to 41.46	24.90 Months Interval 18.99 to 28.12	—	—

SECONDARY outcome

Timeframe: From randomization up to 5 years after the last dose of study drug

Population: ITT Population.

Time to progression is defined as the time from the date of randomization to PD. 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.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Time to Progression, as Assessed by the IRC	42.12 Months Interval 28.94 to 47.67	26.78 Months Interval 22.51 to 31.87	—	—

SECONDARY outcome

Timeframe: From the start of study drug until the start of the next anti-CLL therapy (up to 5 years after the last dose of study drug)

Population: ITT Population

Time to next therapy is defined as the time from randomization until the start of the next-line of treatment. Data are presented for participants who took anti-cancer therapies and participants in the ITT population.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=74 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=67 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Time to Next Therapy	29.68 Months Interval 24.97 to 32.66	21.03 Months Interval 16.79 to 28.35	52.96 Months Interval 43.56 to 62.98	40.08 Months Interval 32.85 to 48.39

SECONDARY outcome

Timeframe: Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day1, follow up (FU) at 1Month (M) after study drug therapy, 3M, then every 3 month up to 5 year (up to 60 months)

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, how the disease affects the daily living, and determines appropriate treatment and prognosis. ECOG performance status are measured at Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1 and Cycle 6 Day1. During follow period, 1 M after study drug therapy, then every 3 month up to 5 year (up to 60 months). Improvement is defined as a decrease from baseline by at least one step on the ECOG performance status scale (yes/no).

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 2 Day 1	15 Participants	13 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 3 Day 1	16 Participants	13 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 4 Day 1	19 Participants	13 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 5 Day 1	20 Participants	15 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 6 Day 1	26 Participants	16 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 1 M, FU	31 Participants	22 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 3 M, FU	31 Participants	21 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 6 M, FU	30 Participants	18 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 9 M, FU	31 Participants	23 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 12 M, FU	30 Participants	20 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 15 M, FU	23 Participants	18 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 18 M, FU	23 Participants	18 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 21 M, FU	22 Participants	16 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 24 M, FU	20 Participants	15 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 27 M, FU	15 Participants	13 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 30 M, FU	14 Participants	8 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 33 M, FU	15 Participants	7 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 36 M, FU	12 Participants	7 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 39 M, FU	12 Participants	7 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 42 M, FU	11 Participants	6 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 45 M, FU	8 Participants	4 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 48 M, FU	8 Participants	2 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 51 M, FU	7 Participants	3 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 54 M, FU	7 Participants	2 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 57 M, FU	3 Participants	3 Participants	—	—
Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status 60 M, FU	3 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: Screening, Cycle1 Day 1, Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day 1 and During at 1M after study drug therapy, 3M, then every 3 M up to 5 year (up to 60 months)

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Participants with no B-symptoms (B-Sy) (no night sweat, no weight loss, no fever and no extreme fatigue) and at least one indicated B-sy(night sweats, weight loss, fever or extreme fatigue) were presented at Screening, Cycle 1 Day 1, Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day 1 and during follow up period at 1 M after study drug therapy, then every 3 M up to 5 year (up to 60 months).

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Screening, no B-sy	63 Participants	59 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Screening, one B-sy	120 Participants	121 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 1 Day 1, no B-sy	64 Participants	68 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 1 Day 1, one B-sy	115 Participants	111 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 2 Day 1,no B-sy	116 Participants	108 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 2 Day 1, one B-sy	52 Participants	62 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 3 Day 1, no B-sy	131 Participants	116 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 3 Day 1, one B-sy	34 Participants	40 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 4 Day 1, no B-sy	129 Participants	107 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 4 Day 1, one B-sy	25 Participants	25 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 5 Day 1, no B-sy	120 Participants	97 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 5 Day 1, one B-sy	14 Participants	21 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 6 Day 1, no B-sy	111 Participants	82 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time Cycle 6 Day 1, one B-sy	9 Participants	13 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 1 M, FU, no B-sy	141 Participants	116 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 1 M, FU, one B-sy	20 Participants	29 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 3 M, FU, no B-sy	136 Participants	105 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 3 M, FU, one B-sy	17 Participants	14 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 6 M, FU, no B-sy	123 Participants	96 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 6 M, FU, one B-sy	15 Participants	11 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 9 M, FU, no B-sy	116 Participants	87 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 9 M, FU, one B-sy	13 Participants	9 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 12 M, FU, no B-sy	108 Participants	74 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 12 M, FU, one B-sy	11 Participants	13 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 15 M, FU, no B-sy	98 Participants	63 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 15 M, FU, one B-sy	5 Participants	8 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 18 M, FU, no B-sy	93 Participants	58 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 18 M, FU, one B-sy	5 Participants	6 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 21 M, FU, no B-sy	87 Participants	55 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 21 M, FU, one B-sy	7 Participants	5 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 24 M, FU, no B-sy	79 Participants	48 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 24 M, FU, one B-sy	1 Participants	4 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 27 M, FU, no B-sy	71 Participants	41 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 27 M, FU, one B-syn	4 Participants	3 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 30 M, FU, no B-sy	68 Participants	33 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 30 M, FU, one B-sy	2 Participants	2 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 33 M, FU, no B-sy	63 Participants	27 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 33 M, FU, one B-sy	3 Participants	2 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 36 M, FU, no B-sy	56 Participants	23 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 36 M, FU, one B-sy	2 Participants	0 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 39 M, FU, no B-sy	49 Participants	18 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 39 M, FU, one B-sy	3 Participants	0 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 42 M, FU, no B-sy	45 Participants	16 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 42 M, FU, one B-sy	0 Participants	0 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 45 M, FU, no B-sy	41 Participants	14 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 45 M, FU, one B-sy	0 Participants	1 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 48 M, FU, no B-sy	36 Participants	13 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 48 M, FU, one B-sy	1 Participants	0 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 51 M, FU, no B-sy	32 Participants	11 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 51 M, FU, one B-sy	0 Participants	1 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 54 M, FU, no B-sy	30 Participants	10 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 54 M, FU, one B-sy	0 Participants	0 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 57 M, FU, no B-sy	26 Participants	9 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 57 M, FU, one B-sy	0 Participants	0 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 60 M, FU, no B-sy	24 Participants	9 Participants	—	—
Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time 60 M, FU, one B-sy	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: From randomization up to 5 years after last dose of study drug

Population: ITT Population

OR is defined as the number of participants achieving an objective response (complete response \[CR\], CR with incomplete bone marrow recovery \[CRi\], partial response \[PR\], and nodular PR \[nPR\]). 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	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC CR	27 Percentage of participants	7 Percentage of participants	—	—
Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC CRi	2 Percentage of participants	1 Percentage of participants	—	—
Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC nPR	0 Percentage of participants	0 Percentage of participants	—	—
Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC PR	55 Percentage of participants	59 Percentage of participants	—	—
Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC Stable disease	11 Percentage of participants	28 Percentage of participants	—	—
Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC Progressive Disease	0 Percentage of participants	0 Percentage of participants	—	—
Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC Not Evaluable	4 Percentage of participants	2 Percentage of participants	—	—
Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC Missing	1 Percentage of participants	2 Percentage of participants	—	—

SECONDARY outcome

Timeframe: From randomization up to 5 years after last dose of study drug

Population: ITT Population

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Percentage of Participants With the Best OR, as Assessed by the Investigator CR	45 Percentage of participants	24 Percentage of participants	—	—
Percentage of Participants With the Best OR, as Assessed by the Investigator CRi	12 Percentage of participants	4 Percentage of participants	—	—
Percentage of Participants With the Best OR, as Assessed by the Investigator nPR	2 Percentage of participants	8 Percentage of participants	—	—
Percentage of Participants With the Best OR, as Assessed by the Investigator PR	107 Percentage of participants	113 Percentage of participants	—	—
Percentage of Participants With the Best OR, as Assessed by the Investigator Stable disease	9 Percentage of participants	21 Percentage of participants	—	—
Percentage of Participants With the Best OR, as Assessed by the Investigator Progressive Disease	0 Percentage of participants	3 Percentage of participants	—	—
Percentage of Participants With the Best OR, as Assessed by the Investigator Missing	8 Percentage of participants	9 Percentage of participants	—	—
Percentage of Participants With the Best OR, as Assessed by the Investigator Responder	166 Percentage of participants	149 Percentage of participants	—	—

SECONDARY outcome

Timeframe: From randomization up to 5 years after last dose of study drug

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed CR. MRD analysis was performed for the participants who were suspected of achieving a primary endpoint CR. MDR was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC Screening	0 Participants	0 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC Cycle 1 Day 1	0 Participants	—	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 3 M, FU	21 Participants	7 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 6 M, FU	25 Participants	6 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 9 M, FU	20 Participants	4 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 12 M, FU	16 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 15 M, FU	14 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 18 M, FU	12 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 21 M, FU	9 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 24 M, FU	8 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 27 M, FU	8 Participants	0 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 30 M, FU	8 Participants	2 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 33 M, FU	3 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 36 M, FU	5 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 39 M, FU	2 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 42 M, FU	2 Participants	—	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 45 M, FU	1 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 48 M, FU	2 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 51 M, FU	2 Participants	1 Participants	—	—
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC 54 M, FU	2 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: From randomization up to 5 years after last dose of study drug

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants Who Were Negative for MRD Assessed by Investigator Screening	0 Participants	1 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 3 M, FU	39 Participants	15 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 6 M, FU	48 Participants	11 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 9 M, FU	35 Participants	6 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 12 M, FU	31 Participants	3 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 15 M, FU	23 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 18 M, FU	20 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 21 M, FU	16 Participants	3 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 24 M, FU	13 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 27 M, FU	14 Participants	1 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 30 M, FU	12 Participants	3 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 33 M, FU	8 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 36 M, FU	9 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 39 M, FU	6 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 42 M, FU	7 Participants	1 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 45 M, FU	6 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 48 M, FU	6 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 51 M, FU	5 Participants	1 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 54 M, FU	4 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 57 M, FU	3 Participants	2 Participants	—	—
Number of Participants Who Were Negative for MRD Assessed by Investigator 60 M, FU	3 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: From first dose of study medication to 60 Days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE)

Population: Safety Population: Participants who received at least one dose of a study drug.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=181 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=178 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) AE	170 Participants	153 Participants	—	—
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) SAE	108 Participants	86 Participants	—	—

SECONDARY outcome

Timeframe: From start of study drug until 60 days after the last dose of study medication

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles)

Serum samples for analysis of HAHA were collected at Baseline (Screening), after 3 cycles were compelted, after 1 M and 6 M post last dose. All samples were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA-positive.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=181 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=178 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points Screening Visit, n= 179,177	8 Participants	1 Participants	—	—
Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points Cycle 4 Day 1, n= 151,130	0 Participants	2 Participants	—	—
Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points 1 M, FU, n= 148,132	0 Participants	2 Participants	—	—
Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points 3 M, FU, n= 0,1	—	0 Participants	—	—
Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points 6 M, FU, n= 130, 99	2 Participants	0 Participants	—	—
Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points 9 M, FU, n= 0, 2	—	0 Participants	—	—
Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points 30 M, FU, n= 2, 0	0 Participants	—	—	—

SECONDARY outcome

Timeframe: From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE)

Population: Safety Population

AIHA is a condition where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants experienced AIHA are presented.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=181 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=178 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants With Autoimmune Hemolytic Anaemia (AIHA)	3 Participants	2 Participants	—	—

SECONDARY outcome

Population: Safety 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. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Maximum severity grades were evaluated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=181 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=178 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants With Drug Related Infections Reported as AEs and SAEs of Maximum Severity of Grade 3 or Higher AE	19 Participants	11 Participants	—	—
Number of Participants With Drug Related Infections Reported as AEs and SAEs of Maximum Severity of Grade 3 or Higher SAE	25 Participants	21 Participants	—	—

SECONDARY outcome

Population: Safety Population

Participants with at least one Grade 3 or Grade 4 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	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=181 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=178 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression Adverse Events	126 Participants	118 Participants	—	—

SECONDARY outcome

Timeframe: From randomization up to 5 years after last dose of study drug

Population: Safety Population

Participants who received no transfusion and at least one transfusion during the study are presented. Participants who took any blood products or blood supportive care product are included.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=181 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=178 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study At least one transfusion	125 Participants	99 Participants	—	—
Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study No transfusions	56 Participants	79 Participants	—	—

SECONDARY outcome

Timeframe: Baseline, 1M and 6M follow up

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

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. Blood samples were collected from each participant and IgA, IgG, and IgM were measured at Baseline, and 1M and 6M after last dose during follow up period.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=181 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=178 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 6 M, FU, IgA	1.0 Gram per liter Standard Deviation 0.77	1.0 Gram per liter Standard Deviation 0.76	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM Cycle 1 Day 1, IgA	1.0 Gram per liter Standard Deviation 0.74	0.9 Gram per liter Standard Deviation 0.68	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM Cycle 1 Day 1, IgG	8.7 Gram per liter Standard Deviation 5.22	8.2 Gram per liter Standard Deviation 3.86	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM Cycle 1 Day 1, IgM	0.6 Gram per liter Standard Deviation 1.36	0.8 Gram per liter Standard Deviation 1.77	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 1 M, FU, IgA	1.0 Gram per liter Standard Deviation 0.79	1.0 Gram per liter Standard Deviation 0.77	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 1 M, FU, IgG	7.9 Gram per liter Standard Deviation 4.05	7.9 Gram per liter Standard Deviation 3.38	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 1 M, FU, IgM	0.5 Gram per liter Standard Deviation 1.16	0.8 Gram per liter Standard Deviation 1.88	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 6 M, FU, IgG	7.8 Gram per liter Standard Deviation 3.97	8.9 Gram per liter Standard Deviation 4.31	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 6 M, FU, IgM	0.4 Gram per liter Standard Deviation 0.50	1.1 Gram per liter Standard Deviation 1.98	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 9 M, FU, IgA	0.9 Gram per liter Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	0.9 Gram per liter Standard Deviation 0.21	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 9 M, FU, IgG	15.2 Gram per liter Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	8.8 Gram per liter Standard Deviation 6.87	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 9 M, FU, IgM	0.8 Gram per liter Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	0.2 Gram per liter Standard Deviation 0.04	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 18 M, FU, IgA	—	2.4 Gram per liter Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 18 M, FU, IgG	—	9.1 Gram per liter Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 18 M, FU, IgM	—	1.0 Gram per liter Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 30 M, FU, IgA	1.3 Gram per liter Standard Deviation 1.17	—	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 30 M, FU, IgG	4.7 Gram per liter Standard Deviation 0.33	—	—	—
Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM 30 M, FU, IgM	0.4 Gram per liter Standard Deviation 0.26	—	—	—

SECONDARY outcome

Timeframe: Screening, Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and after last dose at 1 M and then every three months up to 45 M during Follow-up Period

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

CD5+ and CD19+ cells were counted by flow cytometry at Screening (Baseline) on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 during the treatment period and after last dose of study drug at 1 M and then every three month follow up up to 45 M. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline is defined as the assessment closest to but prior to first dose (e.g. day 1 if available, otherwise, screening). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ Cycle 1 Day 1	43180.6 cells/uL Standard Deviation 48784.64	53208.7 cells/uL Standard Deviation 70944.56	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ Cycle 1 Day 15	2656.9 cells/uL Standard Deviation 6418.02	9244.0 cells/uL Standard Deviation 19610.62	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ Cycle 2 Day 1	2057.4 cells/uL Standard Deviation 5525.72	10318.8 cells/uL Standard Deviation 21453.15	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ Cycle 2 Day 15	513.7 cells/uL Standard Deviation 1717.65	6874.4 cells/uL Standard Deviation 20632.64	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ Cycle 3 Day 1	790.0 cells/uL Standard Deviation 2953.42	6423.6 cells/uL Standard Deviation 19725.57	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ Cycle 4 Day 1	402.1 cells/uL Standard Deviation 1768.74	2643.2 cells/uL Standard Deviation 8092.22	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ Cycle 5 Day 1	142.6 cells/uL Standard Deviation 472.24	2838.6 cells/uL Standard Deviation 8314.08	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ Cycle 6 Day 1	109.8 cells/uL Standard Deviation 398.77	3862.7 cells/uL Standard Deviation 13312.14	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 1 M, FU	163.5 cells/uL Standard Deviation 685.41	5514.3 cells/uL Standard Deviation 17369.97	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 3 M, FU	671.3 cells/uL Standard Deviation 2786.99	2604.9 cells/uL Standard Deviation 9229.90	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 6 M, FU	1591.6 cells/uL Standard Deviation 8857.22	2275.6 cells/uL Standard Deviation 5118.00	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 9 M, FU	910.5 cells/uL Standard Deviation 2495.85	3408.4 cells/uL Standard Deviation 7438.45	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 12 M, FU	2303.2 cells/uL Standard Deviation 6675.70	2876.5 cells/uL Standard Deviation 6252.53	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 15 M, FU	3325.8 cells/uL Standard Deviation 8006.48	3072.7 cells/uL Standard Deviation 9038.23	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 18 M, FU	1607.5 cells/uL Standard Deviation 2935.82	4549.8 cells/uL Standard Deviation 8839.23	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 21 M, FU	3830.8 cells/uL Standard Deviation 8989.02	5236.9 cells/uL Standard Deviation 10537.31	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 24 M, FU	1244.6 cells/uL Standard Deviation 1300.01	7843.3 cells/uL Standard Deviation 11897.55	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 27 M, FU	1877.4 cells/uL Standard Deviation 2117.84	6128.0 cells/uL Standard Deviation 9161.38	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 30 M, FU	5029.7 cells/uL Standard Deviation 8266.90	6515.5 cells/uL Standard Deviation 5916.36	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 33 M, FU	14166.8 cells/uL Standard Deviation 20166.09	5208.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 36 M, FU	1187.0 cells/uL Standard Deviation 1407.79	8184.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 39 M, FU	557.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 42 M, FU	1640.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 45 M, FU	4689.0 cells/uL Standard Deviation 1493.41	—	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 48 M FU	27755.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	29155.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—
Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ 54 M FU	189849.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—	—

SECONDARY outcome

Population: Safety Population

CD5- CD19+ cells were counted by flow cytometry at Screening (baseline) at Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 during treatment period and after last dose of study drug at 1 M and then every three month up to 45 M during follow up period. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline is defined as the assessment closest to but prior to first dose (e.g. Day 1 if available otherwise screening). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=181 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=178 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Change From Baseline in Cell Counts, CD5- CD19+ Screening	4817.8 cells/uL Standard Deviation 20948.17	6959.1 cells/uL Standard Deviation 39980.14	—	—
Change From Baseline in Cell Counts, CD5- CD19+ Cycle 1 Day 1	5996.7 cells/uL Standard Deviation 22331.29	2041.3 cells/uL Standard Deviation 4418.63	—	—
Change From Baseline in Cell Counts, CD5- CD19+ Cycle 1 Day 15	239.0 cells/uL Standard Deviation 1052.19	351.7 cells/uL Standard Deviation 1377.56	—	—
Change From Baseline in Cell Counts, CD5- CD19+ Cycle 2 Day 1	115.4 cells/uL Standard Deviation 403.09	465.7 cells/uL Standard Deviation 1610.05	—	—
Change From Baseline in Cell Counts, CD5- CD19+ Cycle 2 Day 15	35.6 cells/uL Standard Deviation 133.75	331.3 cells/uL Standard Deviation 1177.18	—	—
Change From Baseline in Cell Counts, CD5- CD19+ Cycle 3 Day 1	39.5 cells/uL Standard Deviation 144.64	179.7 cells/uL Standard Deviation 520.63	—	—
Change From Baseline in Cell Counts, CD5- CD19+ Cycle 4 Day 1	25.7 cells/uL Standard Deviation 92.88	95.3 cells/uL Standard Deviation 369.19	—	—
Change From Baseline in Cell Counts, CD5- CD19+ Cycle 5 Day 1	15.9 cells/uL Standard Deviation 77.11	195.5 cells/uL Standard Deviation 945.34	—	—
Change From Baseline in Cell Counts, CD5- CD19+ Cycle 6 Day 1	10.0 cells/uL Standard Deviation 29.85	649.7 cells/uL Standard Deviation 3606.28	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 1 M, FU	7.5 cells/uL Standard Deviation 19.54	863.8 cells/uL Standard Deviation 5001.84	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 3 M, FU	40.1 cells/uL Standard Deviation 238.18	172.0 cells/uL Standard Deviation 681.28	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 6 M, FU	21.2 cells/uL Standard Deviation 58.16	50.7 cells/uL Standard Deviation 49.13	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 9 M, FU	85.7 cells/uL Standard Deviation 359.01	92.0 cells/uL Standard Deviation 101.16	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 12 M, FU	89.9 cells/uL Standard Deviation 226.06	220.1 cells/uL Standard Deviation 698.57	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 15 M, FU	67.3 cells/uL Standard Deviation 59.52	94.6 cells/uL Standard Deviation 70.17	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 18 M, FU	126.1 cells/uL Standard Deviation 188.25	92.3 cells/uL Standard Deviation 69.14	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 21 M, FU	375.5 cells/uL Standard Deviation 1307.35	108.3 cells/uL Standard Deviation 95.86	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 24 M, FU	74.0 cells/uL Standard Deviation 57.46	104.5 cells/uL Standard Deviation 70.46	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 27 M, FU	73.9 cells/uL Standard Deviation 60.40	187.5 cells/uL Standard Deviation 200.85	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 30 M, FU	74.2 cells/uL Standard Deviation 58.82	129.5 cells/uL Standard Deviation 5303	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 33 M, FU	41.8 cells/uL Standard Deviation 40.13	1003.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 36 M, FU	107.3 cells/uL Standard Deviation 86.75	1506.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 39 M, FU	13.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 42 M, FU	13.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 45 M, FU	166.5 cells/uL Standard Deviation 222.74	—	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 48 M, FU	6528.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	28.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—
Change From Baseline in Cell Counts, CD5- CD19+ 54 M, FU	690.0 cells/uL Standard Deviation NA No standard deviation was able to be calculated for this data point because only one participant was analyzed.	—	—	—

SECONDARY outcome

Timeframe: From randomization up to 5 years after last dose of study drug

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected for the assessment of the following prognostic markers at BL: immunoglobulin heavy chain variable region(IgVH) homology; Zeta-Chain-Associated Protein Kinase 70(ZAP70), VH3-21 usage; Cytogenetics (by fluorescent in situ hybridization \[FISH\]); beta 2 microglobulin. Cox-regression model was used to explore the relationship between progression-free survival and the following explanatory variables: treatment group, cytogenetics (analyzed by FISH included 6q-,11q-, +12q, 17p-, 13q-) , ZAP-70 (positive, negative or intermediate), VH3-21 usage (Yes and No), IgVH homology (\>98%, 97%-98% and \<97%), beta 2 microglobulin (\>3500 microgram per liter \[µg/L\] and \<=3500 µg/L). For each covariate, a hazard ratio \<1 indicates a lower risk on the first effect tested compared with the other effects tested. Cytogenetics Group (based on \>=20%)=cytogenetics (CY G).

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Prognostic and Biological Markers Correlating With Clinical Response ZAP70 G 1, Negative	14 Participants	13 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response B2 Microglobulin G 1: > 3500 microgram/liter (μg/L	79 Participants	78 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response B2 Microglobulin G 1: <= 3500 ug/L	22 Participants	26 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response CY G 1: 11q-	29 Participants	19 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response CY G 1: 17p-	6 Participants	9 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response CY G 1: 6q- or +12q or 13q-	38 Participants	48 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response CY G 1: no aberration	27 Participants	27 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response VH3-21 Usage Flag: Yes	6 Participants	4 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response VH3-21 Usage Flag: No	93 Participants	96 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response IgVH Homology, <97%	13 Participants	15 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response IgVH Homology, 97%-98%	5 Participants	7 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response IgVH Homology, >98%	80 Participants	78 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response ZAP70 G 1, Intermediate	27 Participants	23 Participants	—	—
Prognostic and Biological Markers Correlating With Clinical Response ZAP70, G1 Positive	60 Participants	65 Participants	—	—

SECONDARY outcome

Timeframe: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.

Population: Participants

The EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life (HRQoL) important in CLL. There are 4 multi-item scales - fatigue (2 items), treatment side effects (\[TSE\], 4 items), disease symptoms (disease effects scale \[DES\], 4 items), and infection scale \[IS\] (4 items) - and single item scales (social activities \[Social Problems (SP) Scale\] and future health worries\[Future Health (FH) Scale\].). These are measured on a four point scale where 1 = not at all and 4 = very much. These scores are transformed to give a rating from 0 - 100, where 0 =no symptoms or problems and 100 = a severe symptoms or problems. EORTC QLQ-CLL16 was assessed at Screening; Cycle 4 Day 1 and during follow-up 1 M and every 3 M up to 24 months. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value was obtained at randomization.

Outcome measures

SECONDARY outcome

Timeframe: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.

Population: ITT Population. Only those participants available at the specified time points were analyzed.

EQ-5D is comprised of a 5-item health status measure and a visual analogue scale (VAS) and is used to generate two scores: the utility score and the thermometer score. The utility score measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (level 1 = no problem; level 2 = some or moderate problem(s) and level 3 = unable, or extreme problems). Responses are typically converted into health utilities or valuations on a scale ranging from 0 (death) to 1 (perfect health). The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A Negative health status describes health state worse than death.Baseline is the most recent, non-missing value prior to or on the first study drug dose date.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS, 21 M, FU	8.1 Score on a scale Standard Deviation 16.42	11.3 Score on a scale Standard Deviation 24.16	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT, Cycle 4 Day 1	0.0 Score on a scale Standard Deviation 0.27	0.0 Score on a scale Standard Deviation 0.21	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT, 1 M, FU	0.1 Score on a scale Standard Deviation 0.22	0.0 Score on a scale Standard Deviation 0.28	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT, 3 M, FU	0.0 Score on a scale Standard Deviation 0.27	0.1 Score on a scale Standard Deviation 0.23	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT, 6 M, FU	0.1 Score on a scale Standard Deviation 0.24	0.1 Score on a scale Standard Deviation 0.24	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT, 9 M, FU	0.1 Score on a scale Standard Deviation 0.26	0.1 Score on a scale Standard Deviation 0.24	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT. 12 M, FU	0.1 Score on a scale Standard Deviation 0.21	0.1 Score on a scale Standard Deviation 0.22	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT, 15 M, FU	0.0 Score on a scale Standard Deviation 0.23	0.1 Score on a scale Standard Deviation 0.24	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT, 18 M, FU	0.1 Score on a scale Standard Deviation 0.21	0.0 Score on a scale Standard Deviation 0.34	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT, 21 M, FU	0.1 Score on a scale Standard Deviation 0.21	0.1 Score on a scale Standard Deviation 0.26	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit UT, 24 M, FU	0.1 Score on a scale Standard Deviation 0.19	0.1 Score on a scale Standard Deviation 0.28	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS Cycle 4 Day 1	6.1 Score on a scale Standard Deviation 17.68	5.6 Score on a scale Standard Deviation 17.64	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS, 1 M, FU	5.6 Score on a scale Standard Deviation 20.73	5.9 Score on a scale Standard Deviation 22.83	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS, 3 M, FU	5.7 Score on a scale Standard Deviation 19.92	9.6 Score on a scale Standard Deviation 20.88	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS, 6 M, FU	8.2 Score on a scale Standard Deviation 18.84	11.1 Score on a scale Standard Deviation 19.08	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS, 9 M, FU	8.1 Score on a scale Standard Deviation 18.33	11.9 Score on a scale Standard Deviation 20.59	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS. 12 M, FU	7.0 Score on a scale Standard Deviation 21.93	10.3 Score on a scale Standard Deviation 21.21	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS, 15 M, FU	8.0 Score on a scale Standard Deviation 17.52	13.1 Score on a scale Standard Deviation 21.06	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS, 18 M, FU	9.4 Score on a scale Standard Deviation 17.86	11.1 Score on a scale Standard Deviation 25.40	—	—
Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit VAS, 24 M, FU	8.8 Score on a scale Standard Deviation 19.50	15.2 Score on a scale Standard Deviation 21.88	—	—

SECONDARY outcome

Timeframe: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.

Population: ITT Population. Only those participants available at the specified time points were analyzed

EORTC QLQ-C30, a self-reported, cancer-specific instrument assessing 15 domains: physical, role, emotional, cognitive and social functioning, pain,fatigue, nausea and vomiting, insomnia, loss of appetite, constipation, diarrhea, and dyspnea, financial difficulties and a global health status/quality of life (QOF). Functional and symptoms scales were measured on four point Likert scale where 1 = not at all and 4 = very much. Pat. assessed at Screening; Cycle 4 Day 1 and during follow-up 1 M and every 3 M up to 24 months. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Clinically meaningful changes or minimally important differences (MIDs)have been previously established for the EORTC QLQ C30, and categorized as 'small' if the mean change in scores is 5-10 points, 'moderate' if 10-20 points, and 'large' if \>20points.

Outcome measures

SECONDARY outcome

Timeframe: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The HCQ consists of a single question in which the participant is asked if he/she has experienced any change in his/her health overall since beginning the study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for 'my health is a great deal better' to 9 for 'my health is a great deal worse' since the beginning of the study. Lower scores represent better conditions.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects n=182 Participants Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Mean of Health Change Questionnaire (HCQ) Cycle 4 Day 1	2.6 Unit on a scale Standard Deviation 1.62	2.8 Unit on a scale Standard Deviation 1.59	—	—
Mean of Health Change Questionnaire (HCQ) 1 M, FU	3.0 Unit on a scale Standard Deviation 2.05	3.2 Unit on a scale Standard Deviation 2.30	—	—
Mean of Health Change Questionnaire (HCQ) 3 M, FU	3.0 Unit on a scale Standard Deviation 2.11	2.8 Unit on a scale Standard Deviation 1.86	—	—
Mean of Health Change Questionnaire (HCQ) 6 M, FU	2.6 Unit on a scale Standard Deviation 1.76	2.6 Unit on a scale Standard Deviation 1.82	—	—
Mean of Health Change Questionnaire (HCQ) 9 M, FU	2.5 Unit on a scale Standard Deviation 1.78	2.4 Unit on a scale Standard Deviation 1.57	—	—
Mean of Health Change Questionnaire (HCQ) 12 M, FU	2.5 Unit on a scale Standard Deviation 1.80	2.5 Unit on a scale Standard Deviation 1.78	—	—
Mean of Health Change Questionnaire (HCQ) 15 M, FU	2.2 Unit on a scale Standard Deviation 1.57	2.3 Unit on a scale Standard Deviation 1.68	—	—
Mean of Health Change Questionnaire (HCQ) 18 M, FU	2.4 Unit on a scale Standard Deviation 1.67	2.7 Unit on a scale Standard Deviation 2.01	—	—
Mean of Health Change Questionnaire (HCQ) 21 M, FU	2.3 Unit on a scale Standard Deviation 1.50	2.3 Unit on a scale Standard Deviation 1.52	—	—
Mean of Health Change Questionnaire (HCQ) 24 M, FU	2.3 Unit on a scale Standard Deviation 1.76	2.6 Unit on a scale Standard Deviation 1.89	—	—

SECONDARY outcome

Timeframe: Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5,6

Population: PK Population: Participants for whom a pharmacokinetic sample was obtained were analyzed, only participants available at the specified time points were analyzed(represented by n=X in the category titles)

Area under the time-concentration curve (AUC) over the dosing interval (AUC\[0-tau\]) was evaluated. Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, predose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, and 6 (Days 29, 57, 113, and 141).

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab cycle 4	89091.35 hournanogram/mililiter (hng/mL) Interval 78326.34 to 101335.9	—	—	—
Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab cycle 5	96829.23 hournanogram/mililiter (hng/mL) Interval 84488.81 to 110972.1	—	—	—
Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab cycle 6	104798.0 hournanogram/mililiter (hng/mL) Interval 90904.74 to 120814.6	—	—	—
Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab cycle 2	67069.79 hournanogram/mililiter (hng/mL) Interval 59485.45 to 75621.13	—	—	—
Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab cycle 1, week 1	3554.910 hournanogram/mililiter (hng/mL) Interval 3224.844 to 3918.759	—	—	—
Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab cycle 1, week 2	34109.67 hournanogram/mililiter (hng/mL) Interval 30042.08 to 38728.0	—	—	—
Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab cycle 3	84620.05 hournanogram/mililiter (hng/mL) Interval 76209.86 to 93958.35	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5

Blood samples were collected to assess the plasma concentration of ofatumumab.Cmax and Ctrough were determined. Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, predose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, and 6 (Days 29, 57, 113, and 141).

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab Cmax cycle 1, week 1	61.355 Micrograms per milliliter Interval 55.444 to 67.897	—	—	—
Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab Cmax cycle 1, week 2	241.192 Micrograms per milliliter Interval 210.492 to 276.369	—	—	—
Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab Cmax cycle 4	312.745 Micrograms per milliliter Interval 287.708 to 339.961	—	—	—
Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab Ctrough cycle 1, week 1	3.551 Micrograms per milliliter Interval 2.417 to 5.217	—	—	—
Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab Ctrough cycle 1, week 2	9.496 Micrograms per milliliter Interval 6.565 to 13.736	—	—	—
Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab Ctrough cycle 2	24.281 Micrograms per milliliter Interval 17.953 to 32.84	—	—	—
Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab Ctrough cycle 3	25.632 Micrograms per milliliter Interval 18.884 to 34.791	—	—	—
Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab Ctrough cycle 4	58.640 Micrograms per milliliter Interval 44.465 to 77.333	—	—	—
Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab Ctrough cycle 5	70.398 Micrograms per milliliter Interval 55.257 to 89.686	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Week 1, Cycle 1 Week 2, Cycle 4

Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4.

Outcome measures

Outcome measures
Measure	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects n=183 Participants Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared \[m\^2\] and cyclophosphamide was administered at 250mg/m\^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.	Fludarabine + Cyclophosphamide_ ITT Subjects Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m\^2 and cyclophosphamide administered at 250mg/m\^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Time of Occurrence of Cmax (Tmax) of Ofatumumab cycle 1, week 1	6.106 Hour Interval 5.789 to 6.442	—	—	—
Time of Occurrence of Cmax (Tmax) of Ofatumumab cycle 1, week 2	5.004 Hour Interval 4.896 to 5.114	—	—	—
Time of Occurrence of Cmax (Tmax) of Ofatumumab cycle 4	4.878 Hour Interval 4.661 to 5.105	—	—	—

Adverse Events

Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects

Serious events: 108 serious events

Other events: 149 other events

Deaths: 40 deaths

Fludarabine + Cyclophosphamide_ ITT Subjects

Serious events: 86 serious events

Other events: 123 other events

Deaths: 42 deaths

Serious adverse events

Other adverse events

Additional Information

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