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

NCT ID: NCT00910910

Last Updated: 2019-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 450 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-13
• Study Completion Date: 2018-05-09

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.

Conditions

B-Cell Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1 - Lenalidomide

1 - Lenalidomide

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

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.

2- Chlorambucil

2- Chlorambucil

Group Type: ACTIVE_COMPARATOR

Chlorambucil

Intervention Type: DRUG

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).

Interventions

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.

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Revlimid; Leukeran

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]

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Jones, MD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

California Cancer Associates for Research and Excellence cCARE

Escondido, California, United States

Innovative Clinical Research Institute

Whittier, California, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Cancer Center of Central Connecticut

Southington, Connecticut, United States

University Hematology Oncology Inc.

Centralia, Illinois, United States

North Chicago VA Medical Center

North Chicago, Illinois, 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

Purchase Cancer Group

Paducah, Kentucky, United States

University of Minnesota

Minneapolis, Minnesota, United States

Saint Louis University Cancer Center

St Louis, Missouri, United States

Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Oncology and Hematology Associates, PA

Denville, New Jersey, United States

The Cancer Center, Hackensack University Medical Center

Hackensack, New Jersey, United States

Somerset Hematology-Oncology Associates

Somerville, New Jersey, United States

Roswell Park Cancer Center

Buffalo, New York, United States

New York Medical College

Valhalla, New York, United States

Gabrail Cancer Center Research

Canton, Ohio, United States

Drexel University, College of Medicine

Philadelphia, Pennsylvania, United States

Pottstown Memorial Medical Center

Pottstown, Pennsylvania, United States

Berks Hematology-Oncology Associates

West Reading, Pennsylvania, United States

Geisinger Health System

Wilkes-Barre, Pennsylvania, United States

Charleston Hematology Oncology P.A.

Charleston, South Carolina, United States

South Carolina Cancer Specialists

Hilton Head Island, South Carolina, United States

Central Texas Veterans Health Care System

Temple, Texas, United States

Swedish Tumor Institute

Seattle, Washington, United States

Providence St. Mary Regional Cancer Center

Walla Walla, Washington, United States

Columbia St Marys Cancer Center

Milwaukee, Wisconsin, United States

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

IMVS

Adelaide, South Australia, Australia

Western Hospital

Footscray, Victoria, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Flinders Medical Centre

Bedford Park, , Australia

St. Vincent Hospital

Fitzroy, , Australia

Nepean Hospital

Kingswood, NSW, , Australia

Calvary Mater Hospital

Waratah, , Australia

Westmead Hospital Australia

Westmead, , Australia

Universitaetsklinik Innsbruck

Innsbruck, , Austria

Medical University of Vienna Internalmedicine 1, Hematology

Vienna, , Austria

Institut Jules Bordet

Brussels, , Belgium

Hopital Erasme

Brussels, , Belgium

Hopital de Jolimont

Haine-Saint-Paul, , Belgium

AZ Groeninge

Kortrijk, , Belgium

UZ Leuven

Leuven, , Belgium

CHU Mont -Godinne

Yvoir, , Belgium

Monte Tabor - Hospital Sao Rafael

Salvador, Estado de Bahia, Brazil

BIOCANCER - Centro de Pesquisa e Tratamento do Câncer S/A

Belo Horizonte, Minas Gerais, 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

Fundacao Pio XII - Hospital de Cancer de Barretos

Barretos, São Paulo, 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

Instituto Estadual Arthur de Siqueira Cavalcanti - HEMORIO

Rio de Janeiro, , Brazil

Instituto Nacional de Cancer - INCA

Rio de Janeiro, , Brazil

Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC

Santo André, , Brazil

Instituto de Ensino e Pesquisa Sao Lucas

São Paulo, , Brazil

Fundação Antonio Prudente - AC Camargo Câncer center

São Paulo, , Brazil

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, , Bulgaria

Regional Health Authority B-Saint John Regional Hospital

Saint John, New Brunswick, Canada

General Hospital, Eastern Health

St. John's, Newfoundland and Labrador, Canada

Hospital Charles LeMoyne

Greenfield Park, Quebec, Canada

Sacre-Couer Hospital

Montreal, Quebec, Canada

Instituto Oncologico

Reñaca, , Chile

Instituto Clinico Oncologico del Sur ICOS

Temuco, , Chile

Oncomedica S.A.

Montería, , Colombia

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, , Croatia

University Hospital2.Dep.Intern.Med. Hematology

Hradec Králové, , Czechia

Fakultni nemocnice Ostrava

Ostrava, , Czechia

Faculty Hospital Kralovske Vinohrady

Prague, , Czechia

Rigshospitalet University Hospital

Copenhagen, , Denmark

Herlev University Hospital Dep of hematology

Harlev, , Denmark

Roskilde University Hospital

Roskilde, , Denmark

Bergonie Institut

Bordeaux, , France

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

CHRU

Grenoble, , France

CHU Dupuytren

Limoges, , France

Hopital de l'Archet 1

Nice, , France

CHU Hautepierre

Strasbourg, , France

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum

Debrecen, , Hungary

Kaposi Mor Oktato Korhaz

Kaposvár, , Hungary

Szegedi TudomanyegyetemII Belgyogyaszati Klinika

Szeged, , Hungary

Komarom-Esztergom Megye Onkormanyzat Szent Borbala Korhaza

Tatabánya, , Hungary

Petz Aladar Country Hospital

Vasvari Pal U. 2, , Hungary

Ha'Emek Medical Center

Afula, , Israel

Barzilai Medical Center

Ashkelon, , Israel

Soroka University Medical Center

Beersheba, , Israel

Bnei Zion Medical Center

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Meir Medical Center

Kfar Saba, , Israel

Western Galilee Hospital

Nahariya, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

Tel Aviv Sourasky Medical Center Department of Hematology

Tel Aviv, , Israel

Sheba Medical Center

Tel Litwinsky, , Israel

Azienda Ospedaliera Policlinico di Bari

Bari, , Italy

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

IRCSS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

Milan, , Italy

Ospedale San Raffaele S.r.l.

Milan, , Italy

Istituto Europeo di Oncologia - IEO

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

Padua, , 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, , Italy

Maxima Medisch Centrum

Eindhoven, , Netherlands

Spaame Ziekenhuis

Hoofddorp, , Netherlands

Isala Klinieken

Zwolle, , Netherlands

Christchurch Hospital

Christchurch, , New Zealand

North Shore University Hospital

Takapuna, , New Zealand

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

Warsaw, , Poland

Nowotworww Krwi i Transplantacji Szpiku

Wroclaw, , Poland

Hospitais da Universidade de Coimbra

Coimbra, , Portugal

Instituto Portugues Oncologia do Porto Francisco Gentil EPE

Porto, , Portugal

Institutul Clinic Fundeni

Bucharest, , Romania

Spitalul Clinic Coltea

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi

Iași, , Romania

Spitalul Clinic Judetean de Urgenta Sibiu

Sibiu, , Romania

Spitalul Clinic Municipal de Urgenta Timisoara

Timișoara, , Romania

Archangelsk Regional Clinical Hospital

Arkhangelsk, , Russia

City Hospital 8

Barnaul, , Russia

Russian Academy of Medical Sciences Institution

Moscow, , Russia

Moscow GUZ City Clinical Hospital

Moscow, , Russia

NUZ Central Clinical Hospital

Moscow, , Russia

GUZ Nizhegorodskaya Regional Clinical Hospital

Nizhny Novgorod, , Russia

MUZ City clinical hospital

Novosibirsk, , Russia

St. Petersburg Research Institute of Hematology and Blood Transfusion

Saint Petersburg, , Russia

GUS Leningrad Regional Clinical Hospital

Saint Petersburg, , Russia

Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov

Saint Petersburg, , Russia

Regional Clinical Hospital 1

Yekaterinburg, , Russia

Clinical Center Kragujevac

Kragujevac, , Serbia

Clinical Center Nis

Niš, , Serbia

Narodny onkologicky ustav

Bratislava, , Slovakia

Martinska Fakultna Nemocnica

Martin, , Slovakia

University Witwatersrand Oncology

Parktown, , South Africa

Pretoria Academic Hospital

Pretoria, , South Africa

Mary Potter Oncology Centre

Pretoria, , South Africa

Hospital Germans Trias I Pujol

Badalona, , Spain

Hospital Universitario Vall D hebron

Barcelona, , Spain

Hospital Donostia

Donostia / San Sebastian, , Spain

Hospital Universitario de la Princesa

Madrid, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, , Spain

Hospital General Universitario Morales Messeguer

Murcia, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Royal Bournemouth General Hospital

Bournemouth, , United Kingdom

St. Bartholomew's and The Royal London Hospital

London, , United Kingdom

St George's Healthcare NHS Trust

London, , United Kingdom

Countries

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

References

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.

Reference Type: RESULT

PMID: 28140392 (View on PubMed)

Related Links

https://www.nature.com/articles/leu201747

Related Info

Other Identifiers

2008-003079-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-5013-CLL-008

Identifier Type: -

Identifier Source: org_study_id