Trial Outcomes & Findings for Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy (NCT NCT01646021)

Last Updated: 2018-01-19

Results Overview

PFS is defined as the duration in months from the date of randomization to the date of progression disease (PD) or relapse from complete response (CR) or death whichever was reported first and was assessed based on the investigator assessment. Revised Response Criteria for Malignant Lymphoma categorizes the response of the treatment of a patient's tumour to CR (the disappearance of all evidence of disease), Relapsed Disease or PD (Any new lesion or increase by greater than or equal to \[\>=\] 50 percent \[%\] of previously involved sites from nadir).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

280 participants

Primary outcome timeframe

Time from the date of randomization until the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever occurred first (approximately 48 months)

Results posted on

2018-01-19

Participant Flow

139 participants were randomized and treated in the ibrutinib arm and 141 participants were randomized to the temsirolimus arm.

Participant milestones

Participant milestones
Measure	Ibrutinib Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Study STARTED	139	141
Overall Study Treated	139	139
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	139	141

Reasons for withdrawal

Reasons for withdrawal
Measure	Ibrutinib Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Study Death	77	83
Overall Study Study Terminated by Sponsor	50	41
Overall Study Lost to Follow-up	2	2
Overall Study Withdrawal by Subject	10	15

Baseline Characteristics

Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.	Total n=280 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	53 Participants n=5 Participants	54 Participants n=7 Participants	107 Participants n=5 Participants
Age, Categorical >=65 years	86 Participants n=5 Participants	87 Participants n=7 Participants	173 Participants n=5 Participants
Age, Continuous	66.7 years STANDARD_DEVIATION 8.68 • n=5 Participants	67.1 years STANDARD_DEVIATION 9.83 • n=7 Participants	66.9 years STANDARD_DEVIATION 9.26 • n=5 Participants
Sex/Gender, Customized Female	39 participants n=5 Participants	33 participants n=7 Participants	72 participants n=5 Participants
Sex/Gender, Customized Male	100 participants n=5 Participants	108 participants n=7 Participants	208 participants n=5 Participants
Region of Enrollment Belgium	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment Brazil	5 participants n=5 Participants	10 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Canada	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Colombia	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Czech Republic	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Germany	12 participants n=5 Participants	11 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Spain	5 participants n=5 Participants	14 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment France	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment United Kingdom	11 participants n=5 Participants	16 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Hungary	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Ireland	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Italy	6 participants n=5 Participants	8 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment South Korea	11 participants n=5 Participants	3 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Mexico	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Netherlands	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Poland	9 participants n=5 Participants	14 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Portugal	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Russian Federation	18 participants n=5 Participants	11 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Sweden	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Taiwan	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Ukraine	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: Time from the date of randomization until the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever occurred first (approximately 48 months)

Population: The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Progression Free Survival (PFS)	15.6 Months Interval 10.6 to 25.1	6.2 Months Interval 4.2 to 7.8

SECONDARY outcome

Timeframe: Approximately up to 48 months

Population: The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

ORR is defined as the percentage of participants who achieved either CR or PR as best overall response based on the investigator assessment. CR is Disappearance of all target lesions while PR is greater than or equal to 30 % decrease in the sum of the longest diameter of target lesions and Overall Response (OR) is sum of CR and PR.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Response Rate (ORR)	77.0 Percentage of participants	46.8 Percentage of participants

SECONDARY outcome

Timeframe: Approximately up to 48 months

Population: The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Overall survival (OS) was defined as the interval between the date of randomization and the date of death from any cause.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Survival (OS)	30.3 Months Interval 19.1 to 42.1	23.5 Months Interval 13.0 to 30.7

SECONDARY outcome

Timeframe: Approximately up to 48 months

Population: The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received. The 'N' (number of participants analyzed) signifies the number of participants responded for this outcome measure.

Duration of response (CR or PR), defined as the duration in days from the date of initial response to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death. The analysis was based on the investigator assessment.

Outcome measures

Outcome measures
Measure	Ibrutinib n=107 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=66 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Duration of Response	23.1 Months Interval 16.2 to 28.1	6.3 Months Interval 4.7 to 8.6

SECONDARY outcome

Timeframe: Approximately up to 48 months

Population: The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Time to next treatment was measured from the date of randomization to the start date of any anti-neoplastic treatment subsequent to study treatment.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Time-to-Next Treatment	31.8 Months Interval 23.3 to upper 95%CI was not estimable due to less than 50% participants had events occurred	11.6 Months Interval 8.0 to 13.3

SECONDARY outcome

Timeframe: Approximately up to 48 months

Population: The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Progression-free survival 2 defined as the time interval between the date of randomization and date of event, defined as progressive disease as assessed by investigator that started after the next line of subsequent anti-neoplastic therapy (including cross-over to ibrutinib), death from any cause, or the start of the second subsequent anti-neoplastic therapy if no progressive disease was recorded after the first subsequent anti-neoplastic therapy.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Progression-Free Survival 2	26.2 Months Interval 17.2 to 32.4	15.4 Months Interval 10.2 to 21.3

SECONDARY outcome

Timeframe: Approximately up to 48 months

Population: The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening. Worsening was defined by a 5-point decrease from baseline. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score is the total of reverse scores, range 0 to 60. Higher scores indicate a better quality of life.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Time to Worsening in the Lymphoma Sub Scale of Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)	NA Weeks Interval 81.4 to Here, NA indicates median and upper limit of CI of FACT-Lym was not estimable at final analysis due to less than 50% patients had events occurred.	10.6 Weeks Interval 6.6 to 15.3

SECONDARY outcome

Timeframe: Time from first dose of study drug until the last dose date + 30 days or the start of a subsequent anti-neoplastic therapy, whichever occur earlier (Approximately up to 4 years)

Population: Safety population included all randomized participants who received at least 1 dose of the study drug.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=139 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Number of Participants Affected With Treatment-emergent Adverse Events	139 Participants	138 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately up to 2.8 years

Time to response for participants with CR/PR, defined as the interval between the date of randomization and date of initial documentation of response.

Outcome measures

Outcome measures
Measure	Ibrutinib n=100 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=57 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Time to Response	2.15 Months Interval 0.5 to 10.4	2.14 Months Interval 0.9 to 12.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately up to 46.8 months

Population: Safety Analyses Set (SAS) population includes all the randomized participants who received at least 1 dose of study agent (ibrutinib or temsirolimus) during the treatment phase.

Extent of exposure is defined as the duration of the treatment administered during the study. Duration of exposure is calculated as the number of months between the start and end of treatment.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=139 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Extent of Exposure of Time	14.39 Months Interval 0.0 to 46.8	3.02 Months Interval 0.0 to 31.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Month 12

Population: The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

One -year survival rate, defined as the proportion of participants who were alive 1 year after randomization.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
One Year Survival Rate	0.68 Proportion of participants Interval 0.59 to 0.75	0.61 Proportion of participants Interval 0.52 to 0.69

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle 1 and 2 (Day 1): Predose, 1, 2, 4 hr. postdose; Cycle 3 (day 1): Predose (Each cycle is of 21 days)

Population: Pharmacokinetic analysis set included the participants who had received one dose of study drug had at least 1 pharmacokinetic sample obtained post-treatment.

The AUC-ss is the area under the plasma concentration time curve observed during steady state.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Area Under the Plasma Concentration of Ibrutinib During Steady State (AUC-ss)	561.6 nanogramhour per milliliter (ngh/mL) Standard Deviation 448	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately up to 28.2 months

Biomarker evaluations to identify markers altering BCR signaling or activate alternative signaling pathways and explore their association with response or resistance to ibrutinib. Next-generation sequencing at baseline identifies possible primary resistance mutations and those found only at progression are acquired mutations on therapy.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Number of Participants With Biomarkers That Alter B-cell Receptor (BCR) Signaling or Activate Alternative Signaling Pathways and to Explore Their Association With Response or Resistance to Ibrutinib	61 Participants	53 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately up to 28.2 months

Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.

Outcome measures

Outcome measures
Measure	Ibrutinib n=83 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=91 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Number of Hospitalizations Reported Related Medical Resource Utilization Information (MRUI)	3.1 Hospitalizations Standard Deviation 4.6	2.8 Hospitalizations Standard Deviation 4.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately up to 28.2 months

Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.

Outcome measures

Outcome measures
Measure	Ibrutinib n=5 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=5 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Number of Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI)	1.2 Emergency room visits Standard Deviation 0.4	1.2 Emergency room visits Standard Deviation 0.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately up to 28.2 months

Population: The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.

Outcome measures

Outcome measures
Measure	Ibrutinib n=139 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=141 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Days of Hospitalization and Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI) Mean days of hospitalization	19.7 Days Standard Deviation 20.5	20.3 Days Standard Deviation 22.4
Days of Hospitalization and Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI) Mean days of emergency room visits	1.8 Days Standard Deviation 1.3	1.6 Days Standard Deviation 1.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Cycle 2, 3, 4, 5, 6, 7, 8, 11, 14, 17, 20, 28, 36 and End of treatment (approximately up to 23 months)

The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression, using 5 levels (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and possible total score range -0.594 to 1; higher score indicates a better health state.

Outcome measures

Adverse Events

Ibrutinib

Serious events: 79 serious events

Other events: 130 other events

Deaths: 130 deaths

Temsirolimus

Serious events: 83 serious events

Other events: 137 other events

Deaths: 137 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Clinical Research

Janssen-Cilag International NV

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ibrutinib n=138 Participants Participants received 560 milligram (mg) ibrutinib (4\*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.	Temsirolimus n=130 Participants Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 7	0.0 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 8	0.0 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 11	0.0 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 14	0.0 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.1
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 17	0.0 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 20	0.0 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 28	-0.1 Units on scale Standard Deviation 0.2	0.1 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 36	0.0 Units on scale Standard Deviation 0.3	-0.1 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at End of treatment	0.0 Units on scale Standard Deviation 0.2	-0.1 Units on scale Standard Deviation 0.3
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Baseline	0.7 Units on scale Standard Deviation 0.2	0.7 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 2	0.0 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 3	0.1 Units on scale Standard Deviation 0.2	-0.1 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 4	0.0 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.3
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 5	0.0 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.2
The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment Change at Cycle 6	0.1 Units on scale Standard Deviation 0.2	0.0 Units on scale Standard Deviation 0.2