Clinical trial NCT00910910: Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: B-Cell Chronic Lymphocytic Leukemia
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2009-06-01
Enrollment: 450
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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 \[i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia\]

Primary outcomes:
measure: Kaplan-Meier Estimate of Progression Free Survival (PFS)
timeFrame: From first dose of study drug to date of data cut-off of 18 Feb 2013; up to approximately 39 months
measure: Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off Date of 14 March 2014
timeFrame: From randomization to data cut off date of 31 March 2014; median follow up time for all participants was 12.6 months
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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
measure: Number of Participants With Adverse Events With a Later Cut-off Date of 31 March 2014
timeFrame: 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
measure: Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines
timeFrame: Up to data cut-off date of 18 Feb 2013; approximately 39 months
measure: Percentage of Participants With a Best Overall Response Based on IWCLL Guidelines With a Later Cut-off Date of 31 March 2014
timeFrame: Up to data cut-off of 31 March 2014; approximately 53 months
measure: Kaplan-Meier Estimate for Duration of Response
timeFrame: Up to data cut-off of 18 Feb 2013; up to approximately 39 months
measure: Kaplan-Meier Estimate for Duration of Response With a Later Cut-off Date of 31 March 2014
timeFrame: Up to data cut-off of 31 March 2014; up to approximately 53 months
measure: Time to Response
timeFrame: Up to data cut-off of 18 Feb 2013; up to approximately 39 months
measure: Time to Response for a Later Cut-off Date of 31 March 2014
timeFrame: Up to data cut-off of 31 March 2014; up to approximately 53 months
measure: Kaplan Meier Estimate of Overall Survival
timeFrame: Up to data cut off of 31 March 2014; median follow-up for all participants was 18.8 months
measure: Kaplan Meier Estimate for Overall Survival at the Final Analysis
timeFrame: Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
measure: Functional Assessment of Cancer Therapy-General to Create the FACT-Leukemia (FACT-Leu) Quality of Life Instrument
timeFrame: Day 1 and once every 8 weeks
measure: Euro Quality of Life Five Dimension (EQ-5D) Questionnaire
timeFrame: Day 1 and once every 8 weeks
measure: Number of Participants and Types of Subsequent Anti-cancer Therapies Received Post Treatment
timeFrame: Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
Other outcomes:
measure: Number of Participants Deaths During the Treatment and Survival Follow-Up Phase
timeFrame: 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
Locations:
city: Escondido
country: United States
facility: California Cancer Associates for Research and Excellence cCARE
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Southington
country: United States
facility: Cancer Center of Central Connecticut
state: Connecticut
city: Centralia
country: United States
facility: University Hematology Oncology Inc.
state: Illinois
city: North Chicago
country: United States
facility: North Chicago VA Medical Center
state: Illinois
city: Muncie
country: United States
facility: Medical Consultants, PC
state: Indiana
city: New Albany
country: United States
facility: Floyd Memorial Cancer Center of Indiana, a division of Floyd Memorial Hospital and Health Services
state: Indiana
city: Paducah
country: United States
facility: Purchase Cancer Group
state: Kentucky
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation
state: Nevada
city: Denville
country: United States
facility: Oncology and Hematology Associates, PA
state: New Jersey
city: Hackensack
country: United States
facility: The Cancer Center, Hackensack University Medical Center
state: New Jersey
city: Somerville
country: United States
facility: Somerset Hematology-Oncology Associates
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Philadelphia
country: United States
facility: Drexel University, College of Medicine
state: Pennsylvania
city: Pottstown
country: United States
facility: Pottstown Memorial Medical Center
state: Pennsylvania
city: West Reading
country: United States
facility: Berks Hematology-Oncology Associates
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Health System
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology P.A.
state: South Carolina
city: Hilton Head Island
country: United States
facility: South Carolina Cancer Specialists
state: South Carolina
city: Temple
country: United States
facility: Central Texas Veterans Health Care System
state: Texas
city: Seattle
country: United States
facility: Swedish Tumor Institute
state: Washington
city: Walla Walla
country: United States
facility: Providence St. Mary Regional Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Columbia St Marys Cancer Center
state: Wisconsin
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: IMVS
state: South Australia
city: Footscray
country: Australia
facility: Western Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Fitzroy
country: Australia
facility: St. Vincent Hospital
city: Kingswood, NSW
country: Australia
facility: Nepean Hospital
city: Waratah
country: Australia
facility: Calvary Mater Hospital
city: Westmead
country: Australia
facility: Westmead Hospital Australia
city: Innsbruck
country: Austria
facility: Universitaetsklinik Innsbruck
city: Vienna
country: Austria
facility: Medical University of Vienna Internalmedicine 1, Hematology
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Erasme
city: Haine-Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Yvoir
country: Belgium
facility: CHU Mont -Godinne
city: Salvador
country: Brazil
facility: Monte Tabor - Hospital Sao Rafael
state: Bahia
city: Belo Horizonte
country: Brazil
facility: BIOCANCER - Centro de Pesquisa e Tratamento do Câncer S/A
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Fundacao Pio XII - Hospital de Cancer de Barretos
state: São Paulo
city: Brasílía
country: Brazil
facility: Hospital Universitario de Brasilia
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
city: Londrina
country: Brazil
facility: Pro Onco Centro de Tratamento Oncologico
city: Morumbi
country: Brazil
facility: Hospital Israelita Albert Einstein
city: Rio de Janeiro
country: Brazil
facility: Instituto Estadual Arthur de Siqueira Cavalcanti - HEMORIO
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer - INCA
city: Santo Andre
country: Brazil
facility: Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC
city: São Paulo
country: Brazil
facility: Instituto de Ensino e Pesquisa Sao Lucas
city: São Paulo
country: Brazil
facility: Fundação Antonio Prudente - AC Camargo Câncer center
city: Pleven
country: Bulgaria
facility: MHAT Georgi Stranski PlevenHematology Clinic
city: Plovdiv
country: Bulgaria
facility: University hospital Sveti Georgi Hematology Clinic
city: Sofia
country: Bulgaria
facility: Military Medical Academy
city: Sofia
country: Bulgaria
facility: National Specialized Hospital for Active Treatment of Hematology Diseases
city: Varna
country: Bulgaria
facility: University hospital Sveta Marina
city: Saint John
country: Canada
facility: Regional Health Authority B-Saint John Regional Hospital
state: New Brunswick
city: St John's
country: Canada
facility: General Hospital, Eastern Health
state: Newfoundland and Labrador
city: Greenfield Park
country: Canada
facility: Hospital Charles LeMoyne
state: Quebec
city: Montreal
country: Canada
facility: Sacre-Couer Hospital
state: Quebec
city: Renaca
country: Chile
facility: Instituto Oncologico
city: Temuco
country: Chile
facility: Instituto Clinico Oncologico del Sur ICOS
city: Monteria
country: Colombia
facility: Oncomedica S.A.
city: Split
country: Croatia
facility: University Hospital Centre Split
city: Zagreb
country: Croatia
facility: General Hospital Sveti Duh
city: Zagreb
country: Croatia
facility: Klinicka bolnica Dubrava Klinika za unutarnje bolesti Odjel za Hematologiju
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Hradec Kralove
country: Czechia
facility: University Hospital2.Dep.Intern.Med. Hematology
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Prague
country: Czechia
facility: Faculty Hospital Kralovske Vinohrady
city: Copenhagen
country: Denmark
facility: Rigshospitalet University Hospital
city: Harlev
country: Denmark
facility: Herlev University Hospital Dep of hematology
city: Roskilde
country: Denmark
facility: Roskilde University Hospital
city: Bordeaux
country: France
facility: Bergonie Institut
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Grenoble cedex 09
country: France
facility: CHRU
city: Limoges
country: France
facility: CHU Dupuytren
city: Nice
country: France
facility: Hopital de l'Archet 1
city: Strasbourg
country: France
facility: CHU Hautepierre
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
city: Kaposvar
country: Hungary
facility: Kaposi Mor Oktato Korhaz
city: Szeged
country: Hungary
facility: Szegedi TudomanyegyetemII Belgyogyaszati Klinika
city: Tatabanya
country: Hungary
facility: Komarom-Esztergom Megye Onkormanyzat Szent Borbala Korhaza
city: Vasvari Pal U. 2
country: Hungary
facility: Petz Aladar Country Hospital
city: Afula
country: Israel
facility: Ha'Emek Medical Center
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Bnei Zion Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Kfar-Saba
country: Israel
facility: Meir Medical Center
city: Naharia
country: Israel
facility: Western Galilee Hospital
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center Department of Hematology
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico di Bari
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milan
country: Italy
facility: IRCSS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
city: Milan
country: Italy
facility: Ospedale San Raffaele S.r.l.
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia - IEO
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria di Modena
city: Naples
country: Italy
facility: Ospedale Cardarelli
city: Novara
country: Italy
facility: Universita del Piemonte Orientale
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga
city: Padova
country: Italy
facility: Universita degli Studi di Padova
city: Pisa
country: Italy
facility: Ospedale S. Chiara
city: Potenza
country: Italy
facility: Azienda Ospedaliera Ospedale San Carlo
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Torrette Di Ancona
country: Italy
facility: Ospedale Umberto I
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Hoofddorp
country: Netherlands
facility: Spaame Ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala Klinieken
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Takapuna
country: New Zealand
facility: North Shore University Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Wojewodzki Szpital Specjalistczny im. Mikolaja Kopernika
city: Torun
country: Poland
facility: Specjalistyczny Szpital miejski im. Kopernika
city: Warszawa
country: Poland
facility: Klinika Chorob wewnetrznych i Hematologii
city: Wroclaw
country: Poland
facility: Nowotworww Krwi i Transplantacji Szpiku
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Porto
country: Portugal
facility: Instituto Portugues Oncologia do Porto Francisco Gentil EPE
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni
city: Bucharest
country: Romania
facility: Spitalul Clinic Coltea
city: Iasi
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi
city: Sibiu
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Sibiu
city: Timisoara
country: Romania
facility: Spitalul Clinic Municipal de Urgenta Timisoara
city: Arkhangelsk
country: Russian Federation
facility: Archangelsk Regional Clinical Hospital
city: Barnaul
country: Russian Federation
facility: City Hospital 8
city: Ekaterinburg
country: Russian Federation
facility: Regional Clinical Hospital 1
city: Moscow
country: Russian Federation
facility: Russian Academy of Medical Sciences Institution
city: Moscow
country: Russian Federation
facility: Moscow GUZ City Clinical Hospital
city: Moscow
country: Russian Federation
facility: NUZ Central Clinical Hospital
city: Nizhniy Novgorod
country: Russian Federation
facility: GUZ Nizhegorodskaya Regional Clinical Hospital
city: Novosibirsk
country: Russian Federation
facility: MUZ City clinical hospital
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Research Institute of Hematology and Blood Transfusion
city: St. Petersburg
country: Russian Federation
facility: GUS Leningrad Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Nis
country: Serbia
facility: Clinical Center Nis
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
city: Martin
country: Slovakia
facility: Martinska Fakultna Nemocnica
city: Parktown
country: South Africa
facility: University Witwatersrand Oncology
city: Pretoria
country: South Africa
facility: Pretoria Academic Hospital
city: Pretoria
country: South Africa
facility: Mary Potter Oncology Centre
city: Badalona
country: Spain
facility: Hospital Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D hebron
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Messeguer
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: San Sebastian
country: Spain
facility: Hospital Donostia
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth General Hospital
city: London
country: United Kingdom
facility: St. Bartholomew's and The Royal London Hospital
city: London
country: United Kingdom
facility: St George's Healthcare NHS Trust
Study officials:
affiliation: Celgene Corporation
name: Jeffrey Jones, MD
role: STUDY_DIRECTOR
References:
citation: 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.