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

B-Cell Chronic Lymphocytic Leukemia Clinical Trial

— ORIGIN  

Official title:

A Phase 3, Multicenter, Randomized, Openlabel, Parallel-Group Study of the Efficacy and Safety of Lenalidomide (Revlimid®) Versus Chlorambucil as First-Line Therapy for Previously Untreated Elderly Patients With B-Cell Chronic Lymphocytic Leukemia (The Origin Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00910910
• Other study ID #: CC-5013-CLL-008
• Secondary ID: 2008-003079-32
• Status: Completed
• Phase: Phase 3
• Start date: October 13, 2009
• Est. completion date: May 9, 2018

Study information

• Verified date: June 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and efficacy of lenalidomide as a first line therapy in treating patients with B-cell Chronic Lymphocytic Leukemia. This study will compare the effects (good and bad) of lenalidomide with chlorambucil.

Description:

After notification from the US Food and Drug Administration (FDA) on 12 July 2013, Celgene agreed to discontinue the lenalidomide treatment for all patients due to an imbalance in the number of deaths in patients treated with lenalidomide versus patients treated with chlorambucil. No specific causality for this imbalance has been identified to date. Investigators were instructed to immediately discontinue all participants from experimental lenalidomide treatment and inform their patients accordingly. Participants on the Chlorambucil arm may continue up to 12 months (13 cycles) with the last participant completing in March 2014. All randomized participants will continue to be followed for overall survival and secondary primary malignancies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 450
• Est. completion date: May 9, 2018
• Est. primary completion date: March 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

1. Must sign an informed consent form.

2. Age = 65 years

3. Must be able to adhere to the study visit schedule and other protocol requirements.

4. Must have a documented diagnosis of B-cell CLL.

5. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of =2.

6. Must agree to follow pregnancy precautions as required by the protocol.

7. Must agree to receive counseling related to teratogenic and other risks of lenalidomide.

8. Must agree not to donate blood or semen as defined by the protocol

Exclusion Criteria:

1. Prior treatment for B-cell CLL.

2. Any medical condition, that would prevent the subject from signing the informed consent form.

3. Active infections requiring systemic antibiotics.

4. Systemic infection that has not resolved > 2 months prior to initiating lenalidomide

5. Pregnant or lactating females.

6. Participation in any clinical study or having taken any investigational therapy within 28 days.

7. Known presence of alcohol and/or drug abuse.

8. Central nervous system (CNS) involvement.

9. Prior history of malignancies, other than CLL, unless the subject has been free of the disease for =3 years. Exceptions include the following:

• Basal cell carcinoma of the skin

• Squamous cell carcinoma of the skin

• Carcinoma in situ of the cervix

• Carcinoma in situ of the breast

• Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)

10. History of renal failure requiring dialysis.

11. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection.

12. Prior therapy with lenalidomide.

13. Evidence of TLS at screening

14. Presence of specific hematology and/or chemistry abnormalities

15. Uncontrolled hyperthyroidism or hypothyroidism

16. Venous thromboembolism within one year

17. = Grade-2 neuropathy

18. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia

19. Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia]

Related Conditions & MeSH terms

• B-Cell Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Lenalidomide
For patients with normal renal function (defined as CrCl = 60 mL/min), 5 mg once daily on Days 1 through 28 of the first 28-day cycle, 10 mg once daily on Days 1 through 28 starting at the second cycle, 15 mg once daily starting at the third cycle and for the remainder of the study until PD or unacceptable toxicity, whichever occurs first. For patients with moderate renal impairment (defined as CrCl = 30 to < 60 mL/min), 2.5 mg once daily on Days 1 through 28 of the first 28-day cycle, 5 mg once daily on Days 1 through 28 starting at the second cycle, 7.5 mg once daily starting at the third cycle and for the remainder of the study until PD or unacceptable toxicity, whichever occurs first.
• Chlorambucil
Patients assigned to the chlorambucil arm will receive oral chlorambucil tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).

Locations

Country	Name	City	State
Australia	IMVS	Adelaide	South Australia
Australia	Flinders Medical Centre	Bedford Park
Australia	St. Vincent Hospital	Fitzroy
Australia	Western Hospital	Footscray	Victoria
Australia	Nepean Hospital	Kingswood, NSW
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	Calvary Mater Hospital	Waratah
Australia	Westmead Hospital Australia	Westmead
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Universitaetsklinik Innsbruck	Innsbruck
Austria	Medical University of Vienna Internalmedicine 1, Hematology	Vienna
Belgium	Hopital Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Hopital de Jolimont	Haine-Saint Paul
Belgium	AZ Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	CHU Mont -Godinne	Yvoir
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos	Barretos	São Paulo
Brazil	BIOCANCER - Centro de Pesquisa e Tratamento do Câncer S/A	Belo Horizonte	Minas Gerais
Brazil	Hospital Universitario de Brasilia	Brasílía
Brazil	Hospital Erasto Gaertner	Curitiba
Brazil	Pro Onco Centro de Tratamento Oncologico	Londrina
Brazil	Hospital Israelita Albert Einstein	Morumbi
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Estadual Arthur de Siqueira Cavalcanti - HEMORIO	Rio de Janeiro
Brazil	Instituto Nacional de Cancer - INCA	Rio de Janeiro
Brazil	Monte Tabor - Hospital Sao Rafael	Salvador	Bahia
Brazil	Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC	Santo Andre
Brazil	Fundação Antonio Prudente - AC Camargo Câncer center	São Paulo
Brazil	Instituto de Ensino e Pesquisa Sao Lucas	São Paulo
Bulgaria	MHAT Georgi Stranski PlevenHematology Clinic	Pleven
Bulgaria	University hospital Sveti Georgi Hematology Clinic	Plovdiv
Bulgaria	Military Medical Academy	Sofia
Bulgaria	National Specialized Hospital for Active Treatment of Hematology Diseases	Sofia
Bulgaria	University hospital Sveta Marina	Varna
Canada	Hospital Charles LeMoyne	Greenfield Park	Quebec
Canada	Sacre-Couer Hospital	Montreal	Quebec
Canada	Regional Health Authority B-Saint John Regional Hospital	Saint John	New Brunswick
Canada	General Hospital, Eastern Health	St John's	Newfoundland and Labrador
Chile	Instituto Oncologico	Renaca
Chile	Instituto Clinico Oncologico del Sur ICOS	Temuco
Colombia	Oncomedica S.A.	Monteria
Croatia	University Hospital Centre Split	Split
Croatia	General Hospital Sveti Duh	Zagreb
Croatia	Klinicka bolnica Dubrava Klinika za unutarnje bolesti Odjel za Hematologiju	Zagreb
Croatia	University Hospital Centre Zagreb	Zagreb
Czechia	University Hospital2.Dep.Intern.Med. Hematology	Hradec Kralove
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Faculty Hospital Kralovske Vinohrady	Prague
Denmark	Rigshospitalet University Hospital	Copenhagen
Denmark	Herlev University Hospital Dep of hematology	Harlev
Denmark	Roskilde University Hospital	Roskilde
France	Bergonie Institut	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	CHRU	Grenoble cedex 09
France	CHU Dupuytren	Limoges
France	Hopital de l'Archet 1	Nice
France	CHU Hautepierre	Strasbourg
Hungary	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum	Debrecen
Hungary	Kaposi Mor Oktato Korhaz	Kaposvar
Hungary	Szegedi TudomanyegyetemII Belgyogyaszati Klinika	Szeged
Hungary	Komarom-Esztergom Megye Onkormanyzat Szent Borbala Korhaza	Tatabanya
Hungary	Petz Aladar Country Hospital	Vasvari Pal U. 2
Israel	Ha'Emek Medical Center	Afula
Israel	Barzilai Medical Center	Ashkelon
Israel	Soroka University Medical Center	Beer Sheva
Israel	Bnei Zion Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar-Saba
Israel	Western Galilee Hospital	Naharia
Israel	Rabin Medical Center	Petach Tikva
Israel	Kaplan Medical Center	Rehovot
Israel	Tel Aviv Sourasky Medical Center Department of Hematology	Tel Aviv
Israel	Sheba Medical Center	Tel Hashomer
Italy	Azienda Ospedaliera Policlinico di Bari	Bari
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	IRCSS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena	Milan
Italy	Istituto Europeo di Oncologia - IEO	Milan
Italy	Ospedale San Raffaele S.r.l.	Milan
Italy	Azienda Ospedaliero Universitaria di Modena	Modena
Italy	Ospedale Cardarelli	Naples
Italy	Universita del Piemonte Orientale	Novara
Italy	AOU San Luigi Gonzaga	Orbassano
Italy	Universita degli Studi di Padova	Padova
Italy	Ospedale S. Chiara	Pisa
Italy	Azienda Ospedaliera Ospedale San Carlo	Potenza
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte	Siena
Italy	Ospedale Umberto I	Torrette Di Ancona
Netherlands	Maxima Medisch Centrum	Eindhoven
Netherlands	Spaame Ziekenhuis	Hoofddorp
Netherlands	Isala Klinieken	Zwolle
New Zealand	Christchurch Hospital	Christchurch
New Zealand	North Shore University Hospital	Takapuna
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Wojewodzki Szpital Specjalistczny im. Mikolaja Kopernika	Lodz
Poland	Specjalistyczny Szpital miejski im. Kopernika	Torun
Poland	Klinika Chorob wewnetrznych i Hematologii	Warszawa
Poland	Nowotworww Krwi i Transplantacji Szpiku	Wroclaw
Portugal	Hospitais da Universidade de Coimbra	Coimbra
Portugal	Instituto Portugues Oncologia do Porto Francisco Gentil EPE	Porto
Romania	Institutul Clinic Fundeni	Bucharest
Romania	Spitalul Clinic Coltea	Bucharest
Romania	Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Sibiu	Sibiu
Romania	Spitalul Clinic Municipal de Urgenta Timisoara	Timisoara
Russian Federation	Archangelsk Regional Clinical Hospital	Arkhangelsk
Russian Federation	City Hospital 8	Barnaul
Russian Federation	Regional Clinical Hospital 1	Ekaterinburg
Russian Federation	Moscow GUZ City Clinical Hospital	Moscow
Russian Federation	NUZ Central Clinical Hospital	Moscow
Russian Federation	Russian Academy of Medical Sciences Institution	Moscow
Russian Federation	GUZ Nizhegorodskaya Regional Clinical Hospital	Nizhniy Novgorod
Russian Federation	MUZ City clinical hospital	Novosibirsk
Russian Federation	Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov	St. Petersburg
Russian Federation	GUS Leningrad Regional Clinical Hospital	St. Petersburg
Russian Federation	St. Petersburg Research Institute of Hematology and Blood Transfusion	St. Petersburg
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinical Center Nis	Nis
Slovakia	Narodny onkologicky ustav	Bratislava
Slovakia	Martinska Fakultna Nemocnica	Martin
South Africa	University Witwatersrand Oncology	Parktown
South Africa	Mary Potter Oncology Centre	Pretoria
South Africa	Pretoria Academic Hospital	Pretoria
Spain	Hospital Germans Trias I Pujol	Badalona
Spain	Hospital Universitario Vall D hebron	Barcelona
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario Puerta de Hierro-Majadahonda	Majadahonda
Spain	Hospital General Universitario Morales Messeguer	Murcia
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Donostia	San Sebastian
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Universitario La Fe	Valencia
United Kingdom	Royal Bournemouth General Hospital	Bournemouth
United Kingdom	St George's Healthcare NHS Trust	London
United Kingdom	St. Bartholomew's and The Royal London Hospital	London
United States	Roswell Park Cancer Center	Buffalo	New York
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	University Hematology Oncology Inc.	Centralia	Illinois
United States	Charleston Hematology Oncology P.A.	Charleston	South Carolina
United States	Oncology and Hematology Associates, PA	Denville	New Jersey
United States	California Cancer Associates for Research and Excellence cCARE	Escondido	California
United States	The Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey
United States	South Carolina Cancer Specialists	Hilton Head Island	South Carolina
United States	Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Columbia St Marys Cancer Center	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Medical Consultants, PC	Muncie	Indiana
United States	Floyd Memorial Cancer Center of Indiana, a division of Floyd Memorial Hospital and Health Services	New Albany	Indiana
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	North Chicago VA Medical Center	North Chicago	Illinois
United States	Purchase Cancer Group	Paducah	Kentucky
United States	Drexel University, College of Medicine	Philadelphia	Pennsylvania
United States	Pottstown Memorial Medical Center	Pottstown	Pennsylvania
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Swedish Tumor Institute	Seattle	Washington
United States	Somerset Hematology-Oncology Associates	Somerville	New Jersey
United States	Cancer Center of Central Connecticut	Southington	Connecticut
United States	Central Texas Veterans Health Care System	Temple	Texas
United States	New York Medical College	Valhalla	New York
United States	Providence St. Mary Regional Cancer Center	Walla Walla	Washington
United States	Berks Hematology-Oncology Associates	West Reading	Pennsylvania
United States	Innovative Clinical Research Institute	Whittier	California
United States	Geisinger Health System	Wilkes-Barre	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Croatia,  Czechia,  Denmark,  France,  Hungary,  Israel,  Italy,  Netherlands,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  United Kingdom, 

References & Publications (1)

Chanan-Khan A, Egyed M, Robak T, Martinelli de Oliveira FA, Echeveste MA, Dolan S, Desjardins P, Blonski JZ, Mei J, Golany N, Zhang J, Gribben JG. Randomized phase 3 study of lenalidomide versus chlorambucil as first-line therapy for older patients with c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants Deaths During the Treatment and Survival Follow-Up Phase	The number of study participants deaths during the treatment and follow-up phase	From the first dose of study drug up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
Primary	Kaplan-Meier Estimate of Progression Free Survival (PFS)	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	From first dose of study drug to date of data cut-off of 18 Feb 2013; up to approximately 39 months
Primary	Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off Date of 14 March 2014	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.	From randomization to data cut off date of 31 March 2014; median follow up time for all participants was 12.6 months
Secondary	Number of Participants With Adverse Events (AEs)	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	From randomization up to data cut-off of 18 Feb 2013; Up to approximately 39 months; maximum duration of exposure for Lenalidomide was 1086 days and 406 days for Chlorambucil
Secondary	Number of Participants With Adverse Events With a Later Cut-off Date of 31 March 2014	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	From randomization to the data cut-off date of 31 March 2014; Up to 53 months; maximum duration of exposure for Lenalidomide was 1140 days and 406 days for Chlorambucil
Secondary	Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines	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	Up to data cut-off date of 18 Feb 2013; approximately 39 months
Secondary	Percentage of Participants With a Best Overall Response Based on IWCLL Guidelines With a Later Cut-off Date of 31 March 2014	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	Up to data cut-off of 31 March 2014; approximately 53 months
Secondary	Kaplan-Meier Estimate for Duration of Response	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	Up to data cut-off of 18 Feb 2013; up to approximately 39 months
Secondary	Kaplan-Meier Estimate for Duration of Response With a Later Cut-off Date of 31 March 2014	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	Up to data cut-off of 31 March 2014; up to approximately 53 months
Secondary	Time to Response	Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines	Up to data cut-off of 18 Feb 2013; up to approximately 39 months
Secondary	Time to Response for a Later Cut-off Date of 31 March 2014	Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines	Up to data cut-off of 31 March 2014; up to approximately 53 months
Secondary	Kaplan Meier Estimate of Overall Survival	Overall Survival is defined as the time between randomization and death from any cause.	Up to data cut off of 31 March 2014; median follow-up for all participants was 18.8 months
Secondary	Kaplan Meier Estimate for Overall Survival at the Final Analysis	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.	Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
Secondary	Functional Assessment of Cancer Therapy-General to Create the FACT-Leukemia (FACT-Leu) Quality of Life Instrument	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).	Day 1 and once every 8 weeks
Secondary	Euro Quality of Life Five Dimension (EQ-5D) Questionnaire	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.	Day 1 and once every 8 weeks
Secondary	Number of Participants and Types of Subsequent Anti-cancer Therapies Received Post Treatment	Subsequent anti-cancer therapies administered to participants following the discontinuation of study drug (either Lenalidomide or Chlorambucil)	Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months

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