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

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)

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.

Study Overview

• Status: Completed
• Conditions: B-Cell Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Lenalidomide; Drug: Chlorambucil

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • Fitzroy, Australia, 3065
    • St. Vincent Hospital
  • Kingswood, NSW, Australia, 2751
    • Nepean Hospital
  • Waratah, Australia, 2298
    • Calvary Mater Hospital
  • Westmead, Australia, NSW2145
    • Westmead Hospital Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • IMVS
  • Victoria
    • Footscray, Victoria, Australia, 3011
      • Western Hospital
    • Melbourne, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Austria
  • Innsbruck, Austria, 6020
    • Universitaetsklinik Innsbruck
  • Vienna, Austria, 1190
    • Medical University of Vienna Internalmedicine 1, Hematology
• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Brussels, Belgium, 1070
    • Hôpital Erasme
  • Haine-Saint Paul, Belgium, 7100
    • Hôpital de Jolimont
  • Kortrijk, Belgium, 8500
    • Az Groeninge
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Yvoir, Belgium, 5530
    • CHU Mont -Godinne
• Brazil
  • Brasílía, Brazil, 70840-050
    • Hospital Universitário de Brasília
  • Curitiba, Brazil, 81520-060
    • Hospital Erasto Gaertner
  • Londrina, Brazil, 86050-190
    • Pro Onco Centro de Tratamento Oncologico
  • Morumbi, Brazil, 05651-901
    • Hospital Israelita Albert Einstein
  • Rio de Janeiro, Brazil, 20230-130
    • Instituto Nacional de Câncer - INCA
  • Rio de Janeiro, Brazil, 20211-030
    • Instituto Estadual Arthur de Siqueira Cavalcanti - HEMORIO
  • Santo Andre, Brazil, 09060-650
    • Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC
  • São Paulo, Brazil, 01509-900
    • Fundação Antônio Prudente - AC Camargo Câncer Center
  • São Paulo, Brazil, 01236-030
    • Instituto de Ensino e Pesquisa São Lucas
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
      • Monte Tabor - Hospital Sao Rafael
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-281
      • BIOCANCER - Centro de Pesquisa e Tratamento do Câncer S/A
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora Da Conceicao
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Fundação Pio XII - Hospital de Câncer de Barretos
• Bulgaria
  • Pleven, Bulgaria, 5800
    • MHAT Georgi Stranski PlevenHematology Clinic
  • Plovdiv, Bulgaria, 4002
    • University hospital Sveti Georgi Hematology Clinic
  • Sofia, Bulgaria, 1606
    • Military Medical Academy
  • Sofia, Bulgaria, 1756
    • National Specialized Hospital for Active Treatment of Hematology Diseases
  • Varna, Bulgaria, 9010
    • University hospital Sveta Marina
• Canada
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Regional Health Authority B-Saint John Regional Hospital
  • Newfoundland and Labrador
    • St John's, Newfoundland and Labrador, Canada, A1B 3V6
      • General Hospital, Eastern Health
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V2H1
      • Hospital Charles LeMoyne
    • Montreal, Quebec, Canada, H4J 1C5
      • Sacre-Couer Hospital
• Chile
  • Renaca, Chile, 2540364
    • Instituto Oncologico
  • Temuco, Chile, 4810469
    • Instituto Clinico Oncologico del Sur ICOS
• Colombia
  • Monteria, Colombia
    • Oncomedica S.A.
• Croatia
  • Split, Croatia, 21000
    • University Hospital Centre Split
  • Zagreb, Croatia, 10000
    • General Hospital Sveti Duh
  • Zagreb, Croatia, 10000
    • University Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • Klinicka bolnica Dubrava Klinika za unutarnje bolesti Odjel za Hematologiju
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • University Hospital2.Dep.Intern.Med. Hematology
  • Ostrava, Czechia, 70852
    • Fakultni Nemocnice Ostrava
  • Prague, Czechia, 100 00
    • Faculty Hospital Kralovske Vinohrady
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet University Hospital
  • Harlev, Denmark, 2730
    • Herlev University Hospital Dep of hematology
  • Roskilde, Denmark, 4000
    • Roskilde University Hospital
• France
  • Bordeaux, France, 33300
    • Polyclinique Bordeaux Nord Aquitaine
  • Bordeaux, France, 33076
    • Bergonié Institut
  • Grenoble cedex 09, France, 38043
    • CHRU
  • Limoges, France, 87042
    • CHU Dupuytren
  • Nice, France, 06200
    • Hôpital de l'Archet 1
  • Strasbourg, France, 67098
    • CHU HautePierre
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
  • Kaposvar, Hungary, 7400
    • Kaposi Mór Oktató Kórház
  • Szeged, Hungary, 6720
    • Szegedi TudomanyegyetemII Belgyogyaszati Klinika
  • Tatabanya, Hungary
    • Komarom-Esztergom Megye Onkormanyzat Szent Borbala Korhaza
  • Vasvari Pal U. 2, Hungary, 9023
    • Petz Aladar Country Hospital
• Israel
  • Afula, Israel, 18101
    • Ha'Emek Medical Center
  • Ashkelon, Israel, 78278
    • Barzilai Medical Center
  • Beer Sheva, Israel, 84101
    • Soroka University Medical Center
  • Haifa, Israel, 31048
    • Bnei Zion Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Kfar-Saba, Israel, 44281
    • Meir Medical Center
  • Naharia, Israel, 22100
    • Western Galilee Hospital
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center Department of Hematology
  • Tel Hashomer, Israel, 52621
    • Sheba Medical Center
• Italy
  • Bari, Italy, 70124
    • Azienda Ospedaliera Policlinico di Bari
  • Firenze, Italy, 50134
    • Azienda Ospedaliera Universitaria Careggi
  • Milan, Italy, 20132
    • Ospedale San Raffaele s.r.l.
  • Milan, Italy, 20122
    • IRCSS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
  • Milan, Italy, 20141
    • Istituto Europeo Di Oncologia - IEO
  • Modena, Italy, 41100
    • Azienda Ospedaliero Universitaria di Modena
  • Naples, Italy, 80131
    • Ospedale Cardarelli
  • Novara, Italy, 28100
    • Università del Piemonte orientale
  • Orbassano, Italy, 10043
    • AOU San Luigi Gonzaga
  • Padova, Italy, 35128
    • Universita degli Studi di Padova
  • Pisa, Italy, 56126
    • Ospedale S. Chiara
  • Potenza, Italy, 85100
    • Azienda Ospedaliera Ospedale San Carlo
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
  • Torrette Di Ancona, Italy, 60020
    • Ospedale Umberto I
• Netherlands
  • Eindhoven, Netherlands, 5631
    • Maxima Medisch Centrum
  • Hoofddorp, Netherlands, 2135
    • Spaame Ziekenhuis
  • Zwolle, Netherlands, 8025 AB
    • Isala Klinieken
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Takapuna, New Zealand, 1309
    • North Shore University Hospital
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Lodz, Poland, 93-510
    • Wojewodzki Szpital Specjalistczny im. Mikolaja Kopernika
  • Torun, Poland, 87-100
    • Specjalistyczny Szpital miejski im. Kopernika
  • Warszawa, Poland, 00-909
    • Klinika Chorob wewnetrznych i Hematologii
  • Wroclaw, Poland, 50-367
    • Nowotworww Krwi i Transplantacji Szpiku
• Portugal
  • Coimbra, Portugal, 3000-075
    • Hospitais da universidade de Coimbra
  • Porto, Portugal, 4200-072
    • Instituto Portugues Oncologia do Porto Francisco Gentil EPE
• Romania
  • Bucharest, Romania, 022328
    • Institutul Clinic Fundeni
  • Bucharest, Romania, 030171
    • Spitalul Clinic Coltea
  • Iasi, Romania, 700111
    • Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi
  • Sibiu, Romania, 550245
    • Spitalul Clinic Judetean de Urgenta Sibiu
  • Timisoara, Romania, 300079
    • Spitalul Clinic Municipal de Urgenta Timisoara
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Archangelsk Regional Clinical Hospital
  • Barnaul, Russian Federation, 659010
    • City Hospital 8
  • Ekaterinburg, Russian Federation, 620102
    • Regional Clinical Hospital 1
  • Moscow, Russian Federation, 115478
    • Russian Academy of Medical Sciences Institution
  • Moscow, Russian Federation, 129128
    • NUZ Central Clinical Hospital
  • Moscow, Russian Federation, 125284
    • Moscow GUZ City Clinical Hospital
  • Nizhniy Novgorod, Russian Federation, 603126
    • GUZ Nizhegorodskaya Regional Clinical Hospital
  • Novosibirsk, Russian Federation, 630051
    • MUZ City Clinical Hospital
  • St. Petersburg, Russian Federation, 191024
    • St. Petersburg Research Institute of Hematology and Blood Transfusion
  • St. Petersburg, Russian Federation, 197341
    • Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov
  • St. Petersburg, Russian Federation, 194291
    • GUS Leningrad Regional Clinical Hospital
• Serbia
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Nis, Serbia, 18000
    • Clinical Center Nis
• Slovakia
  • Bratislava, Slovakia, 83101
    • Narodny onkologicky ustav
  • Martin, Slovakia, 03659
    • Martinska Fakultna Nemocnica
• South Africa
  • Parktown, South Africa, 2193
    • University Witwatersrand Oncology
  • Pretoria, South Africa
    • Mary Potter Oncology Centre
  • Pretoria, South Africa, 0002
    • Pretoria Academic Hospital
• Spain
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d Hebron
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro-Majadahonda
  • Murcia, Spain, 30008
    • Hospital General Universitario Morales Messeguer
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • San Sebastian, Spain, 20014
    • Hospital Donostia
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Valencia, Spain, 46009
    • Hospital Universitario La Fe
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth General Hospital
  • London, United Kingdom, SW17 0QT
    • St George's Healthcare NHS Trust
  • London, United Kingdom, EC1A 7BE
    • St. Bartholomew's and The Royal London Hospital
• United States
  • California
    • Escondido, California, United States, 92025
      • California Cancer Associates for Research and Excellence cCARE
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Connecticut
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
    • Southington, Connecticut, United States, 06489
      • Cancer Center of Central Connecticut
  • Illinois
    • Centralia, Illinois, United States, 62801
      • University Hematology Oncology Inc.
    • North Chicago, Illinois, United States, 60064
      • North Chicago VA Medical Center
  • Indiana
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, Pc
    • New Albany, Indiana, United States, 47150
      • Floyd Memorial Cancer Center of Indiana, a division of Floyd Memorial Hospital and Health Services
  • Kentucky
    • Paducah, Kentucky, United States, 42001
      • Purchase Cancer Group
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455-0392
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Research Foundation
  • New Jersey
    • Denville, New Jersey, United States, 07834
      • Oncology and Hematology Associates, PA
    • Hackensack, New Jersey, United States, 07601
      • The Cancer Center, Hackensack University Medical Center
    • Somerville, New Jersey, United States, 08876
      • Somerset Hematology-Oncology Associates
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Center
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University, College of Medicine
    • Pottstown, Pennsylvania, United States, 19464
      • Pottstown Memorial Medical Center
    • West Reading, Pennsylvania, United States, 19611
      • Berks Hematology-Oncology Associates
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Health System
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Charleston Hematology Oncology P.A.
    • Hilton Head Island, South Carolina, United States, 29926
      • South Carolina Cancer Specialists
  • Texas
    • Temple, Texas, United States, 76504
      • Central Texas Veterans Health Care System
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Tumor Institute
    • Walla Walla, Washington, United States, 99362
      • Providence St. Mary Regional Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia St Marys Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 - Lenalidomide	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.; Other Names: Revlimid
Active Comparator: 2- Chlorambucil	Drug: 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).; Other Names: Leukeran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Jeffrey Jones, MD, Celgene Corporation

Publications and helpful links

General Publications

• 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 chronic lymphocytic leukemia (the ORIGIN trial). Leukemia. 2017 May;31(5):1240-1243. doi: 10.1038/leu.2017.47. Epub 2017 Jan 31. No abstract available.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2009
• Primary Completion (Actual): March 31, 2014
• Study Completion (Actual): May 9, 2018

Study Registration Dates

• First Submitted: May 28, 2009
• First Submitted That Met QC Criteria: May 29, 2009
• First Posted (Estimate): June 1, 2009

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: June 14, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Chlorambucil
• Other Study ID Numbers: CC-5013-CLL-008; 2008-003079-32 (EudraCT Number)