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

Condition(s) targeted: B-Cell Chronic Lymphocytic Leukemia (B-CLL)

Intervention: Lenalidomide (Drug); Chlorambucil (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Celgene Corporation

Official(s) and/or principal investigator(s):
Oliver Kong, MD, Study Director, Affiliation: Celgene Corporation

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.

Official title: A PHASE 3, MULTICENTER, RANDOMIZED, OPEN-LABEL, 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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Progression Free Survival (PFS)

Safety [type, frequency, and severity of adverse events (AEs)]

Overall Survival

Number of anti-cancer therapies obtained from randomized participants

Secondary outcome:

Response, including evaluation of minimal residual disease (MRD) by flow cytometry (Hallek, 2008)

Duration of response

Time to response

Health-Related Quality of Life (HRQL) by Functional Assessment of Cancer Therapy -Leukemia (FACT-Leu) and EQ-5D

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.

Minimum age: 65 Years. Maximum age: N/A. Gender(s): Both.

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]

IMVS, Adelaide 5000, 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

Hopital Erasme, Brussels 1070, Belgium

Institut Jules Bordet, Brussels 1000, 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

Hospital Universitario de Brasilia, Brasílía 70840-050, Brazil

Hospital Erasto Gaertner, Curitiba 86050-190, Brazil

Pro Onco Centro de Tratamento Oncológico, 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 Andre 09060-650, Brazil

Fundação Antonio Prudente - AC Camargo Câncer center, São Paulo 01509-900, Brazil

Instituto de Ensino e Pesquisa São Lucas, São Paulo 01236-030, Brazil

MHAT Georgi Stranski PlevenHematology Clinic, Pleven 5800, Bulgaria

University hospital Sveti Georgi Hematology Clinic, Plovdiv 4000, 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

Instituto Oncologico, Renaca 2540364, Chile

Instituto Clinico Oncologico del Sur (ICOS), Temuco 4810469, Chile

Oncomedica S.A., Monteria, 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 Kralove 500 05, Czech Republic

Fakultni nemocnice Ostrava, Ostrava 70852, Czech Republic

Faculty Hospital Kralovske Vinohrady, Prague 100 00, Czech Republic

Rigshospitalet University Hospital, Copenhagen 2100, Denmark

Herlev University Hospital Dep of hematology, Harlev 2730, Denmark

Roskilde University Hospital, Roskilde 4000, Denmark

Clinical Center Kragujevac, Kragujevac 34000, Former Serbia and Montenegro

Clinical Center Nis, Nis 18000, Former Serbia and Montenegro

Bergonie Institut, Bordeaux 33076, France

Polyclinique Bordeaux Nord Aquitaine, Bordeaux 33300, France

CHRU, Grenoble cedex 09 38043, France

CHU Dupuytren, Limoges 87042, France

Hopital de l'Archet 1, Nice 06200, France

CHU Hautepierre, Strasbourg 67098, France

Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Debrecen 4032, Hungary

Kaposi Mor Oktato Korhaz, Kaposvar 7400, Hungary

Szegedi TudomanyegyetemII Belgyogyaszati Klinika, Szeged 6720, Hungary

Komarom-Esztergom Megye Onkormanyzat Szent Borbala Korhaza, Tatabanya, 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, Beer Sheva 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, Naharia 22100, Israel

Rabin Medical Center, Petach 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 Hashomer 52621, Israel

Azienda Ospedaliera Policlinico di Bari, Bari 70124, Italy

Azienda Ospedaliera Universitaria Careggi, Firenze 50134, Italy

IRCSS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan 20122, Italy

Istituto Europeo di Oncologia - IEO, Milan 20141, Italy

Ospedale San Raffaele S.r.l., Milan 20132, 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

Università degli Studi di Padova, Padova 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, Warszawa 00-909, Poland

Nowotworów 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, Oporto 4200-072, Portugal

Institutul Clinic Fundeni, Bucharest 022328, Romania

Spitalul Clinic Coltea, Bucharest 030171, Romania

Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi, Iasi 700111, Romania

Spitalul Clinic Judetean de Urgenta Sibiu, Sibiu 550245, Romania

Spitalul Clinic Municipal de Urgenta Timisoara, Timisoara 300079, Romania

Archangelsk Regional Clinical Hospital, Arkhangelsk 163045, Russian Federation

City Hospital 8, Barnaul 659010, Russian Federation

Regional Clinical Hospital 1, Ekaterinburg 620102, Russian Federation

Moscow GUZ City Clinical Hospital, Moscow 125284, Russian Federation

NUZ Central Clinical Hospital, Moscow 129128, Russian Federation

Russian Academy of Medical Sciences Institution, Moscow 115478, Russian Federation

GUZ Nizhegorodskaya Regional Clinical Hospital, Nizhniy Novgorod 603126, Russian Federation

MUZ City clinical hospital, Novosibirsk 630051, Russian Federation

Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov, St. Petersburg 197341, Russian Federation

GUS Leningrad Regional Clinical Hospital, St. Petersburg 194291, Russian Federation

St. Petersburg Research Institute of Hematology and Blood Transfusion, St. Petersburg 191024, Russian Federation

Narodny onkologicky ustav, Bratislava 83101, Slovakia

Martinska Fakultna Nemocnica, Martin 03659, Slovakia

University Witwatersrand Oncology, Parktown 2193, South Africa

Mary Potter Oncology Centre, Pretoria, South Africa

Pretoria Academic Hospital, Pretoria 0002, South Africa

Hospital Germans Trias I Pujol, Badalona 08916, Spain

Hospital Universitario Vall D hebron, Barcelona 08035, Spain

Hospital Donostia, Donostia 20014, Spain

Hospital Ramon y Cajal, Madrid 28034, Spain

Hospital Universitario de la Princessa, Madrid 28006, 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 George's Healthcare NHS Trust, London SW17 0QT, United Kingdom

St. Bartholomew's and The Royal London Hospital, London EC1A 7BE, United Kingdom

Monte Tabor - Hospital Sao Rafael, Salvador, Bahia 41253-190, Brazil

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

BIOCANCER - Centro de Pesquisa e Tratamento do Câncer S/A, Belo Horizonte, Minas Gerais 30150-281, Brazil

University of Minnesota, Minneapolis, Minnesota 55455-0392, United States

Saint Louis University Cancer Center, Saint Louis, Missouri 63110, United States

Nevada Cancer Research Foundation, Las Vegas, Nevada 89106, United States

Regional Health Authority B-Saint John Regional Hospital, Saint John, New Brunswick E2L 4L2, Canada

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

General Hospital, Eastern Health, St John's, Newfoundland and Labrador A1B 3V6, Canada

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

Hospital Charles LeMoyne, Greenfield Park, Quebec J4V2H1, Canada

Sacre-Couer Hospital, Montreal, Quebec H4J 1C5, Canada

Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia

Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul 90035-903, Brazil

Hospital Nossa Senhora da Conceição, Porto Alegre, Rio Grande do Sul 91350-200, Brazil

Charleston Hematology/Oncology P.A., Charleston, South Carolina 29403, United States

South Carolina Cancer Specialists, Hilton Head Island, South Carolina 29926, United States

Fundacao Pio XII - Hospital de Cancer de Barretos, Barretos, São Paulo 14784-400, Brazil

Central Texas Veterans Health Care System, Temple, Texas 76504, United States

Western Hospital, Footscray, Victoria 3011, Australia

Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia

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

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Starting date: October 2009
Last updated: May 12, 2015