Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial)

Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost 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

Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. Progressive disease included lymphadenopathy, an appearance of any new lesion such as enlarged lymph nodes (> 1.5 cm), splenomegaly, hepatomegaly or other organ infiltrates, an increase by 50% or more in greatest determined diameter of any previous site or an increase by 50% or more in the sum of the product of diameters of multiple nodes. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost 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.

AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death

AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death

A best overall response rate is a CR, CRi, nPR or PR and is defined as:

Complete Remission (CR):

• No lymphadenopathy
• No hepatomegaly or splenomegaly
• Absence of constitutional symptoms
• Polymorphonuclear leukocytes ≥ 1500/ul
• No circulating clonal B-lymphocytes
• Platelets > 100,000/ul
• Hemoglobin > 11.0 g/dl
• Normocellular <30% lymphocytes, no B-lymphoid nodules;

Incomplete Clinical Response (CRi):

• CR without bone marrow biopsy confirmation.

Nodular Partial Response (nPR):

• CR with the presence of residual clonal nodules.

Partial Response (PR) requires:

• ≥ 50% decrease in peripheral blood lymphocyte count
• ≥ 50% reduction in lymphadenopathy
• ≥ 50% reduction in size of liver and/or spleen
• 1 or more of the following:
• Polymorphonuclear leukocytes ≥ 1500/ul
• Platelets >100,000/ul

A best overall response rate is a CR, CRi, nPR or PR and is defined as:

Complete Remission (CR):

• No lymphadenopathy
• No hepatomegaly or splenomegaly
• Absence of constitutional symptoms
• Polymorphonuclear leukocytes ≥ 1500/ul
• No circulating clonal B-lymphocytes
• Platelets > 100,000/ul
• Hemoglobin > 11.0 g/dl
• Normocellular <30% lymphocytes, no B-lymphoid nodules;

Incomplete Clinical Response (CRi):

• CR without bone marrow biopsy confirmation.

Nodular Partial Response:

• CR with the presence of residual clonal nodules.

Partial Response requires:

• ≥ 50% decrease in peripheral blood lymphocyte count
• ≥ 50% reduction in lymphadenopathy
• ≥ 50% reduction in size of liver and/or spleen
• 1 or more of the following:
• Polymorphonuclear leukocytes ≥ 1500/ul
• Platelets >100,000/ul

Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) participants who had not progressed at the time of analysis; 2) participants who had withdrawn consent or were lost to follow-up prior to documentation of progression

Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) patients who had not progressed at the time of analysis; 2) patients who had withdrawn consent or were lost to follow-up prior to documentation of progression

Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines

Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines

Overall Survival is defined as the time between randomization and death from any cause.

Overall Survival is defined as the time between randomization and death from any cause. Overall survival was censored at the last date that the subject was known to be alive for participants who were alive as of the data cutoff date and for participants who were lost to follow-up before death was documented.

The FACT-Leu scale is a valid, reliable, and efficient measure of leukemia-specific health-related quality of life for acute and chronic disease. The FACT-Leu is described as including 27 items that assess 17 physical symptoms (fevers, bleeding, general pain, stomach pain, chills, night sweats, bruising, lymph node swelling, weakness, tiredness, weight loss, appetite, shortness of breath, functional ability, diarrhea, concentration, and mouth sores) and 10 emotional/social concerns (frustration with activity limitation, discouraged by illness, future planning, uncertainty, worry about illness, emotional lability, isolation, infertility concern, family worry, and worry about infections).

The standardized extended version of EQ-5D was designed for the collection of health state values using a visual analogue scale (VAS) rating scale - a vertical 20 cm visual analogue scale with the end points labeled best imaginable health state at the top and worst imaginable health state at the bottom having numeric values of 100 and 0 respectively. The participant is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.

Subsequent anti-cancer therapies administered to participants following the discontinuation of study drug (either Lenalidomide or Chlorambucil)

The number of study participants deaths during the treatment and follow-up phase