Trial Outcomes & Findings for Study of Lenalidomide to Evaluate Safety and Efficacy in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (NCT NCT00963105)

Last Updated: 2018-10-31

Results Overview

Adverse events (AEs) were graded for severity by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 with the exceptions of hematologic toxicities and tumor lysis syndrome, according to the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening or disabling AE Grade 5 = Death The investigator determined the relationship of each AE to study drug based on the timing of the AE and whether other medications, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the observed event.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

104 participants

Primary outcome timeframe

From first dose of study drug to 30 days after the last dose; the maximum duration of treatment was 251, 265, and 267 weeks in the 5 mg, 10 mg, and 15 mg treatment groups respectively.

Results posted on

2018-10-31

Participant Flow

Participants were randomized at 29 sites from North America and Europe.

Participants were randomized (1:1:1) in a double-blind fashion, according to age (\< 65 versus ≥ 65 years) and disease status (relapsed versus refractory) to their last purine-analog or bendamustine-based prior regimen.

Participant milestones

Participant milestones
Measure	Lenalidomide 5 mg Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability. Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug.	Lenalidomide 10 mg Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability. Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug.	Lenalidomide 15 mg Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability. Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug.
Overall Study STARTED	34	35	35
Overall Study Received Treatment	34	34	35
Overall Study COMPLETED	34	35	35
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Lenalidomide to Evaluate Safety and Efficacy in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenalidomide 5 mg n=34 Participants Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 10 mg n=35 Participants Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 15 mg n=35 Participants Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Total n=104 Participants Total of all reporting groups
Age, Continuous	64.0 years STANDARD_DEVIATION 9.46 • n=5 Participants	63.3 years STANDARD_DEVIATION 8.31 • n=7 Participants	63.7 years STANDARD_DEVIATION 7.56 • n=5 Participants	63.6 years STANDARD_DEVIATION 8.39 • n=4 Participants
Age, Customized < 65 years	16 Participants n=5 Participants	19 Participants n=7 Participants	17 Participants n=5 Participants	52 Participants n=4 Participants
Age, Customized ≥ 65 years	18 Participants n=5 Participants	16 Participants n=7 Participants	18 Participants n=5 Participants	52 Participants n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	32 Participants n=4 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	22 Participants n=7 Participants	24 Participants n=5 Participants	72 Participants n=4 Participants
Race/Ethnicity, Customized White	31 Participants n=5 Participants	30 Participants n=7 Participants	33 Participants n=5 Participants	94 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: From first dose of study drug to 30 days after the last dose; the maximum duration of treatment was 251, 265, and 267 weeks in the 5 mg, 10 mg, and 15 mg treatment groups respectively.

Population: Randomized participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Lenalidomide 5 mg n=34 Participants Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 10 mg n=34 Participants Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 15 mg n=35 Participants Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.
Number of Participants With Treatment-emergent Adverse Events AE leading to study drug interruption & reduction	18 Participants	26 Participants	19 Participants
Number of Participants With Treatment-emergent Adverse Events Any adverse events	34 Participants	34 Participants	35 Participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related adverse events (TRAE)	33 Participants	34 Participants	32 Participants
Number of Participants With Treatment-emergent Adverse Events Grade 3/4 adverse events	33 Participants	32 Participants	34 Participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related Grade 3/4 adverse events	31 Participants	32 Participants	30 Participants
Number of Participants With Treatment-emergent Adverse Events Grade 5 adverse events	4 Participants	4 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related Grade 5 adverse events	2 Participants	2 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events Serious adverse events	24 Participants	24 Participants	27 Participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related serious adverse events	15 Participants	13 Participants	20 Participants
Number of Participants With Treatment-emergent Adverse Events AE leading to discontinuation of study drug	21 Participants	17 Participants	16 Participants
Number of Participants With Treatment-emergent Adverse Events TRAE leading to discontinuation of study drug	16 Participants	14 Participants	13 Participants
Number of Participants With Treatment-emergent Adverse Events AE leading to study drug dose reduction only	8 Participants	6 Participants	5 Participants
Number of Participants With Treatment-emergent Adverse Events AE leading to study drug dose interruption only	25 Participants	24 Participants	25 Participants

SECONDARY outcome

Timeframe: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.

Population: All randomized participants (intent-to-treat population)

ORR was defined as the percentage of patients with a complete response (CR), CR with incomplete bone marrow (BM) recovery (CRi) or partial response (PR) during treatment. Response was assessed according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines. Per the guidelines, a CR required peripheral blood lymphocytes below 4 x 10\^9/L, absence of lymphadenopathy, no hepatomegaly or splenomegaly, absence of disease and blood counts neutrophils \>1.5 x 10\^9/L, platelets \>100 x 10\^9/L, hemoglobin (hgb) \>11g/dL) and BM at least normocellular for age. CRi = CR with incomplete BM recovery. PR = required at least 2 months from end of treatment, a ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value and either a ≥ 50% reduction in lymphadenopathy or ≥50% reduction of liver enlargement or ≥50% reduction of spleen enlargement plus neutrophils \>1.5 x 10\^9/ or ≥50% increase, platelets \>100 x 10\^9/L or ≥50% increase, hgb 11 g/dL.

Outcome measures

Outcome measures
Measure	Lenalidomide 5 mg n=34 Participants Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 10 mg n=35 Participants Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 15 mg n=35 Participants Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.
Overall Response Rate (ORR)	47.1 percentage of participants	37.1 percentage of participants	40.0 percentage of participants

SECONDARY outcome

Timeframe: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.

Population: Randomized participants with an objective response (CR/CRi or PR)

Duration of response (DOR) was defined as the time from the first visit where PR, CRi, or CR was documented to progressive disease (PD). Duration of response was censored at the last date that the participant was known to be progression-free for participants who had not progressed at the time of analysis or who withdrew consent or were lost to follow-up prior to documentation of progression.

Outcome measures

Outcome measures
Measure	Lenalidomide 5 mg n=16 Participants Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 10 mg n=13 Participants Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 15 mg n=14 Participants Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.
Kaplan-Meier Estimate of Duration of Response	101.1 weeks Interval 60.6 to 239.3	35.1 weeks Interval 22.0 to Could not be calculated due to the low number of events	88.8 weeks Interval 72.1 to 127.3

SECONDARY outcome

Timeframe: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.

Population: Randomized participants with an objective response (CR/CRi or PR)

Time to response (TTR) was calculated as the time from randomization to the first documented date of response (PR, CRi or CR) based on iwCLL guidelines for participants with an objective response during the treatment period.

Outcome measures

Outcome measures
Measure	Lenalidomide 5 mg n=16 Participants Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 10 mg n=13 Participants Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 15 mg n=14 Participants Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.
Time to Response	16.9 weeks Interval 12.1 to 74.1	12.6 weeks Interval 8.4 to 52.1	12.7 weeks Interval 12.0 to 147.3

SECONDARY outcome

Timeframe: From randomization until the end of the study; maximum time on study was 91 months.

Population: All randomized participants

Time to progression (TTP) was defined as the time from randomization to the first documented progression. For participants who did not progress during the study, TTP was censored at the last adequate response assessment showing evidence of no disease progression.

Outcome measures

Outcome measures
Measure	Lenalidomide 5 mg n=34 Participants Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 10 mg n=35 Participants Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 15 mg n=35 Participants Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.
Kaplan-Meier Estimate of Time to Progression	96.3 weeks Interval 20.6 to 251.3	47.6 weeks Interval 31.9 to 261.1	66.3 weeks Interval 20.1 to 89.3

SECONDARY outcome

Timeframe: From randomization until the end of the study; maximum time on study was 91 months.

Population: All randomized participants

Event-free survival (EFS) is the interval between the start of treatment to the first sign of disease progression, or treatment for relapse or death (whichever occurred first). If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.

Outcome measures

Outcome measures
Measure	Lenalidomide 5 mg n=34 Participants Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 10 mg n=35 Participants Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 15 mg n=35 Participants Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.
Kaplan-Meier Estimate of Event-Free Survival	25.6 weeks Interval 16.1 to 77.6	31.9 weeks Interval 21.1 to 47.6	24.1 weeks Interval 13.4 to 66.3

SECONDARY outcome

Timeframe: From randomization until the end of the study; maximum time on study was 91 months.

Population: All randomized participants

Progression-free survival (PFS) was calculated as the time from randomization to the first documented progression or death due to any cause during or after the treatment period, whichever occurred first. The progression date was assigned to the earliest time when any progression is observed without prior missing assessments. If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.

Outcome measures

Outcome measures
Measure	Lenalidomide 5 mg n=34 Participants Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 10 mg n=35 Participants Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 15 mg n=35 Participants Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.
Kaplan-Meier Estimate of Progression Free Survival	31.4 weeks Interval 16.1 to 96.3	45.1 weeks Interval 22.4 to 120.1	66.3 weeks Interval 16.1 to 89.3

SECONDARY outcome

Timeframe: From randomization until the end of the study; maximum time on study was 91 months.

Population: All randomized participants

Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who had withdrawn consent or were lost to follow-up before death was documented.

Outcome measures

Outcome measures
Measure	Lenalidomide 5 mg n=34 Participants Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 10 mg n=35 Participants Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.	Lenalidomide 15 mg n=35 Participants Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.
Kaplan-Meier Estimate of Overall Survival	161.0 weeks Interval 64.9 to 209.0	106.7 weeks Interval 83.4 to 235.7	154.6 weeks Interval 80.9 to 214.7

Adverse Events

Lenalidomide 5 mg

Serious events: 24 serious events

Other events: 34 other events

Deaths: 24 deaths

Lenalidomide 10 mg

Serious events: 24 serious events

Other events: 34 other events

Deaths: 23 deaths

Lenalidomide 15 mg

Serious events: 27 serious events

Other events: 35 other events

Deaths: 26 deaths

Serious adverse events

Other adverse events

Additional Information

Associate Director, Clinical Trials Disclosure

Celgene Corporation

Phone: 1-888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is \> 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER