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)
2 other identifiers
interventional
450
26 countries
163
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Oct 2009
Longer than P75 for phase_3
163 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 28, 2009
CompletedFirst Posted
Study publicly available on registry
June 1, 2009
CompletedStudy Start
First participant enrolled
October 13, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2014
CompletedResults Posted
Study results publicly available
December 21, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 9, 2018
CompletedJuly 9, 2019
June 1, 2019
4.5 years
May 28, 2009
September 23, 2015
June 14, 2019
Conditions
Outcome Measures
Primary Outcomes (2)
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 Outcomes (13)
Number of Participants With Adverse Events (AEs)
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
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
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
Up to data cut-off of 31 March 2014; approximately 53 months
Kaplan-Meier Estimate for Duration of Response
Up to data cut-off of 18 Feb 2013; up to approximately 39 months
- +8 more secondary outcomes
Other Outcomes (1)
Number of Participants Deaths During the Treatment and Survival 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
Study Arms (2)
1 - Lenalidomide
EXPERIMENTAL1 - Lenalidomide
2- Chlorambucil
ACTIVE COMPARATOR2- Chlorambucil
Interventions
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.
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).
Eligibility Criteria
You may qualify if:
- Must sign an informed consent form.
- Age ≥ 65 years
- Must be able to adhere to the study visit schedule and other protocol requirements.
- Must have a documented diagnosis of B-cell CLL.
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.
- Must agree to follow pregnancy precautions as required by the protocol.
- Must agree to receive counseling related to teratogenic and other risks of lenalidomide.
- Must agree not to donate blood or semen as defined by the protocol
You may not qualify if:
- Prior treatment for B-cell CLL.
- Any medical condition, that would prevent the subject from signing the informed consent form.
- Active infections requiring systemic antibiotics.
- Systemic infection that has not resolved \> 2 months prior to initiating lenalidomide
- Pregnant or lactating females.
- Participation in any clinical study or having taken any investigational therapy within 28 days.
- Known presence of alcohol and/or drug abuse.
- Central nervous system (CNS) involvement.
- 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)
- History of renal failure requiring dialysis.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celgenelead
Study Sites (165)
California Cancer Associates for Research and Excellence cCARE
Escondido, California, 92025, United States
Innovative Clinical Research Institute
Whittier, California, 90603, United States
The Hospital of Central Connecticut
New Britain, Connecticut, 06050, United States
Cancer Center of Central Connecticut
Southington, Connecticut, 06489, United States
University Hematology Oncology Inc.
Centralia, Illinois, 62801, United States
North Chicago VA Medical Center
North Chicago, Illinois, 60064, United States
Medical Consultants, PC
Muncie, Indiana, 47303, United States
Floyd Memorial Cancer Center of Indiana, a division of Floyd Memorial Hospital and Health Services
New Albany, Indiana, 47150, United States
Purchase Cancer Group
Paducah, Kentucky, 42001, United States
University of Minnesota
Minneapolis, Minnesota, 55455-0392, United States
Saint Louis University Cancer Center
St Louis, Missouri, 63110, United States
Nevada Cancer Research Foundation
Las Vegas, Nevada, 89106, United States
Oncology and Hematology Associates, PA
Denville, New Jersey, 07834, United States
The Cancer Center, Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Somerset Hematology-Oncology Associates
Somerville, New Jersey, 08876, United States
Roswell Park Cancer Center
Buffalo, New York, 14263, United States
New York Medical College
Valhalla, New York, 10595, United States
Gabrail Cancer Center Research
Canton, Ohio, 44718, United States
Drexel University, College of Medicine
Philadelphia, Pennsylvania, 19102, United States
Pottstown Memorial Medical Center
Pottstown, Pennsylvania, 19464, United States
Berks Hematology-Oncology Associates
West Reading, Pennsylvania, 19611, United States
Geisinger Health System
Wilkes-Barre, Pennsylvania, 18711, United States
Charleston Hematology Oncology P.A.
Charleston, South Carolina, 29403, United States
South Carolina Cancer Specialists
Hilton Head Island, South Carolina, 29926, United States
Central Texas Veterans Health Care System
Temple, Texas, 76504, United States
Swedish Tumor Institute
Seattle, Washington, 98104, United States
Providence St. Mary Regional Cancer Center
Walla Walla, Washington, 99362, United States
Columbia St Marys Cancer Center
Milwaukee, Wisconsin, 53211, United States
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
IMVS
Adelaide, South Australia, 5000, Australia
Western Hospital
Footscray, Victoria, 3011, Australia
Royal Melbourne Hospital
Melbourne, Victoria, 3050, Australia
Flinders Medical Centre
Bedford Park, 5042, Australia
St. Vincent Hospital
Fitzroy, 3065, Australia
Nepean Hospital
Kingswood, NSW, 2751, Australia
Calvary Mater Hospital
Waratah, 2298, Australia
Westmead Hospital Australia
Westmead, NSW2145, Australia
Universitaetsklinik Innsbruck
Innsbruck, 6020, Austria
Medical University of Vienna Internalmedicine 1, Hematology
Vienna, 1190, Austria
Institut Jules Bordet
Brussels, 1000, Belgium
Hopital Erasme
Brussels, 1070, Belgium
Hopital de Jolimont
Haine-Saint-Paul, 7100, Belgium
AZ Groeninge
Kortrijk, 8500, Belgium
UZ Leuven
Leuven, 3000, Belgium
CHU Mont -Godinne
Yvoir, 5530, Belgium
Monte Tabor - Hospital Sao Rafael
Salvador, Estado de Bahia, 41253-190, Brazil
BIOCANCER - Centro de Pesquisa e Tratamento do Câncer S/A
Belo Horizonte, Minas Gerais, 30150-281, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Hospital Nossa Senhora da Conceicao
Porto Alegre, Rio Grande do Sul, 91350-200, Brazil
Fundacao Pio XII - Hospital de Cancer de Barretos
Barretos, São Paulo, 14784-400, Brazil
Hospital Universitario de Brasilia
Brasílía, 70840-050, Brazil
Hospital Erasto Gaertner
Curitiba, 81520-060, Brazil
Pro Onco Centro de Tratamento Oncologico
Londrina, 86050-190, Brazil
Hospital Israelita Albert Einstein
Morumbi, 05651-901, Brazil
Instituto Estadual Arthur de Siqueira Cavalcanti - HEMORIO
Rio de Janeiro, 20211-030, Brazil
Instituto Nacional de Cancer - INCA
Rio de Janeiro, 20230-130, Brazil
Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC
Santo André, 09060-650, Brazil
Instituto de Ensino e Pesquisa Sao Lucas
São Paulo, 01236-030, Brazil
Fundação Antonio Prudente - AC Camargo Câncer center
São Paulo, 01509-900, Brazil
MHAT Georgi Stranski PlevenHematology Clinic
Pleven, 5800, Bulgaria
University hospital Sveti Georgi Hematology Clinic
Plovdiv, 4002, Bulgaria
Military Medical Academy
Sofia, 1606, Bulgaria
National Specialized Hospital for Active Treatment of Hematology Diseases
Sofia, 1756, Bulgaria
University hospital Sveta Marina
Varna, 9010, Bulgaria
Regional Health Authority B-Saint John Regional Hospital
Saint John, New Brunswick, E2L 4L2, Canada
General Hospital, Eastern Health
St. John's, Newfoundland and Labrador, A1B 3V6, Canada
Hospital Charles LeMoyne
Greenfield Park, Quebec, J4V2H1, Canada
Sacre-Couer Hospital
Montreal, Quebec, H4J 1C5, Canada
Instituto Oncologico
Reñaca, 2540364, Chile
Instituto Clinico Oncologico del Sur ICOS
Temuco, 4810469, Chile
Oncomedica S.A.
Montería, Colombia
University Hospital Centre Split
Split, 21000, Croatia
General Hospital Sveti Duh
Zagreb, 10000, Croatia
Klinicka bolnica Dubrava Klinika za unutarnje bolesti Odjel za Hematologiju
Zagreb, 10000, Croatia
University Hospital Centre Zagreb
Zagreb, 10000, Croatia
University Hospital2.Dep.Intern.Med. Hematology
Hradec Králové, 500 05, Czechia
Fakultni nemocnice Ostrava
Ostrava, 70852, Czechia
Faculty Hospital Kralovske Vinohrady
Prague, 100 00, Czechia
Rigshospitalet University Hospital
Copenhagen, 2100, Denmark
Herlev University Hospital Dep of hematology
Harlev, 2730, Denmark
Roskilde University Hospital
Roskilde, 4000, Denmark
Bergonie Institut
Bordeaux, 33076, France
Polyclinique Bordeaux Nord Aquitaine
Bordeaux, 33300, France
CHRU
Grenoble, 38043, France
CHU Dupuytren
Limoges, 87042, France
Hopital de l'Archet 1
Nice, 06200, France
CHU Hautepierre
Strasbourg, 67098, France
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
Debrecen, 4032, Hungary
Kaposi Mor Oktato Korhaz
Kaposvár, 7400, Hungary
Szegedi TudomanyegyetemII Belgyogyaszati Klinika
Szeged, 6720, Hungary
Komarom-Esztergom Megye Onkormanyzat Szent Borbala Korhaza
Tatabánya, Hungary
Petz Aladar Country Hospital
Vasvari Pal U. 2, 9023, Hungary
Ha'Emek Medical Center
Afula, 18101, Israel
Barzilai Medical Center
Ashkelon, 78278, Israel
Soroka University Medical Center
Beersheba, 84101, Israel
Bnei Zion Medical Center
Haifa, 31048, Israel
Shaare Zedek Medical Center
Jerusalem, 91031, Israel
Meir Medical Center
Kfar Saba, 44281, Israel
Western Galilee Hospital
Nahariya, 22100, Israel
Rabin Medical Center
Petah Tikva, 49100, Israel
Kaplan Medical Center
Rehovot, 76100, Israel
Tel Aviv Sourasky Medical Center Department of Hematology
Tel Aviv, 64239, Israel
Sheba Medical Center
Tel Litwinsky, 52621, Israel
Azienda Ospedaliera Policlinico di Bari
Bari, 70124, Italy
Azienda Ospedaliera Universitaria Careggi
Florence, 50134, Italy
IRCSS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
Milan, 20122, Italy
Ospedale San Raffaele S.r.l.
Milan, 20132, Italy
Istituto Europeo di Oncologia - IEO
Milan, 20141, Italy
Azienda Ospedaliero Universitaria di Modena
Modena, 41100, Italy
Ospedale Cardarelli
Naples, 80131, Italy
Universita del Piemonte Orientale
Novara, 28100, Italy
AOU San Luigi Gonzaga
Orbassano, 10043, Italy
Universita degli Studi di Padova
Padua, 35128, Italy
Ospedale S. Chiara
Pisa, 56126, Italy
Azienda Ospedaliera Ospedale San Carlo
Potenza, 85100, Italy
Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
Siena, 53100, Italy
Ospedale Umberto I
Torrette Di Ancona, 60020, Italy
Maxima Medisch Centrum
Eindhoven, 5631, Netherlands
Spaame Ziekenhuis
Hoofddorp, 2135, Netherlands
Isala Klinieken
Zwolle, 8025 AB, Netherlands
Christchurch Hospital
Christchurch, 8011, New Zealand
North Shore University Hospital
Takapuna, 1309, New Zealand
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952, Poland
Wojewodzki Szpital Specjalistczny im. Mikolaja Kopernika
Lodz, 93-510, Poland
Specjalistyczny Szpital miejski im. Kopernika
Torun, 87-100, Poland
Klinika Chorob wewnetrznych i Hematologii
Warsaw, 00-909, Poland
Nowotworww Krwi i Transplantacji Szpiku
Wroclaw, 50-367, Poland
Hospitais da Universidade de Coimbra
Coimbra, 3000-075, Portugal
Instituto Portugues Oncologia do Porto Francisco Gentil EPE
Porto, 4200-072, Portugal
Institutul Clinic Fundeni
Bucharest, 022328, Romania
Spitalul Clinic Coltea
Bucharest, 030171, Romania
Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi
Iași, 700111, Romania
Spitalul Clinic Judetean de Urgenta Sibiu
Sibiu, 550245, Romania
Spitalul Clinic Municipal de Urgenta Timisoara
Timișoara, 300079, Romania
Archangelsk Regional Clinical Hospital
Arkhangelsk, 163045, Russia
City Hospital 8
Barnaul, 659010, Russia
Russian Academy of Medical Sciences Institution
Moscow, 115478, Russia
Moscow GUZ City Clinical Hospital
Moscow, 125284, Russia
NUZ Central Clinical Hospital
Moscow, 129128, Russia
GUZ Nizhegorodskaya Regional Clinical Hospital
Nizhny Novgorod, 603126, Russia
MUZ City clinical hospital
Novosibirsk, 630051, Russia
St. Petersburg Research Institute of Hematology and Blood Transfusion
Saint Petersburg, 191024, Russia
GUS Leningrad Regional Clinical Hospital
Saint Petersburg, 194291, Russia
Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov
Saint Petersburg, 197341, Russia
Regional Clinical Hospital 1
Yekaterinburg, 620102, Russia
Clinical Center Kragujevac
Kragujevac, 34000, Serbia
Clinical Center Nis
Niš, 18000, Serbia
Narodny onkologicky ustav
Bratislava, 83101, Slovakia
Martinska Fakultna Nemocnica
Martin, 03659, Slovakia
University Witwatersrand Oncology
Parktown, 2193, South Africa
Pretoria Academic Hospital
Pretoria, 0002, South Africa
Mary Potter Oncology Centre
Pretoria, South Africa
Hospital Germans Trias I Pujol
Badalona, 08916, Spain
Hospital Universitario Vall D hebron
Barcelona, 08035, Spain
Hospital Donostia
Donostia / San Sebastian, 20014, Spain
Hospital Universitario de la Princesa
Madrid, 28006, Spain
Hospital Ramon y Cajal
Madrid, 28034, Spain
Hospital Universitario Puerta de Hierro-Majadahonda
Majadahonda, 28222, Spain
Hospital General Universitario Morales Messeguer
Murcia, 30008, Spain
Hospital Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Universitario Marques de Valdecilla
Santander, 39008, Spain
Hospital Universitario La Fe
Valencia, 46009, Spain
Royal Bournemouth General Hospital
Bournemouth, BH7 7DW, United Kingdom
St. Bartholomew's and The Royal London Hospital
London, EC1A 7BE, United Kingdom
St George's Healthcare NHS Trust
London, SW17 0QT, United Kingdom
Related 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 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.
PMID: 28140392RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
After notification by the US Food and Drug Administration on 12Jul2013, Celgene agreed to stop lenalidomide due to an imbalance in the number of deaths on the lenalidomide arm versus the chlorambucil arm; no causality for the imbalance was identified
Results Point of Contact
- Title
- Anne McClain, Senior Manager of Clinical Trial Disclosure
- Organization
- Celgene Corporation
Study Officials
- STUDY DIRECTOR
Jeffrey Jones, MD
Celgene Corporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 28, 2009
First Posted
June 1, 2009
Study Start
October 13, 2009
Primary Completion
March 31, 2014
Study Completion
May 9, 2018
Last Updated
July 9, 2019
Results First Posted
December 21, 2016
Record last verified: 2019-06