Clinical trial NCT00090051: FCR Versus FC Alone in the Treatment of Chronic Lymphocytic Leukemia (CLL) in Relapsed Patients
Official title: Open-label, Multicenter, Randomized, Comparative, Phase III Study to Evaluate the Efficacy and Safety of FCR vs. FC Alone in Previously Treated Patients With CD20 Positive B-cell CLL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Biogen
name: Genentech, Inc.
First posted: 2004-08-25
Enrollment: 552
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to provide treatment for patients who have chronic lymphocytic leukemia (CLL), and to compare the use of rituximab added to fludarabine+cyclophosphamide (FC) with FC alone, to determine if rituximab lengthens the time a patient remains free of leukemia symptoms.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years
* Established diagnosis of B-cell CLL by NCI Working Group criteria
* ≤1 previous line of chemotherapy
* Expected survival \>6 months
* Acceptable hematologic status, liver function, renal function, and pulmonary function
* Negative serum pregnancy test for both pre-menopausal women and for women who are \< 2 years after the onset of menopause
* Written informed consent

Exclusion Criteria:

* Prior treatment with interferon, rituximab or other monoclonal antibody
* Prior allogeneic bone marrow transplant (BMT) or autologous BMT or peripheral stem cell transplant (PBSCT) or patients who are considered to be candidates for allogeneic or autologous BMT or PSCT as assessed by their treating physician
* Fertile men or women of childbearing potential not using adequate contraception
* Severe Grade 3 or 4 non-hematological toxicity or prolonged (\> 2 weeks) Grade 3 or 4 cytopenia on prior fludarabine or nucleoside analogue regimen
* History of fludarabine-induced or clinically significant autoimmune cytopenia
* History of other malignancies within 2 years prior to study entry, except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low-grade early stage localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent.
* Medical conditions requiring long term use (\> 1 month) of systemic corticosteroids
* Active bacterial, viral, or fungal infection requiring systemic therapy
* Severe cardiac disease
* Seizure disorders requiring anticonvulsant therapy
* Severe chronic obstructive pulmonary disease with hypoxemia
* Uncontrolled diabetes mellitus or hypertension
* Transformation to aggressive B-cell malignancy.
* Known infection with HIV, HCV, or hepatitis B
* Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study
* Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins
* Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Primary outcomes:
measure: Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
timeFrame: Mean observation time at time of analysis was approximately 26 months
measure: Number of Participants With Progression-free Survival (PFS) Events Assessed by the Independent Review Committee (IRC)
timeFrame: Mean observation time at time of analysis was approximately 26 months
measure: Final Analysis: Time to Progression-Free Survival Event
timeFrame: Median observation time was approximately 5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Mean observation time at time of analysis was approximately 26 months
measure: Number of Participants With Overall Survival (OS) Events
timeFrame: Mean observation time at time of analysis was approximately 26 months
measure: Event-free Survival (EFS)
timeFrame: Mean observation time at time of analysis was approximately 26 months
measure: Number of Participants With Event-free Survival (EFS) Events
timeFrame: Mean observation time at time of analysis was approximately 26 months
measure: Disease-free Survival (DFS)
timeFrame: Mean observation time at time of analysis was approximately 26 months
measure: Number of Participants With Disease-free Survival (DFS) Events
timeFrame: Mean observation time at time of analysis was approximately 26 months
measure: Final Analysis: Time to Overall Survival Event
timeFrame: Median observation time was approximately 5 years
measure: Final Analysis: Time to Event-Free Survival Event
timeFrame: Median observation time was approximately 5 years
measure: Final Analysis: Percentage of Participants With Complete Response
timeFrame: Median observation time was approximately 5 years
measure: Final Analysis: Time to Disease-Free Survival Event
timeFrame: Median observation time was approximately 5 years
measure: Final Analysis: Duration of Response
timeFrame: Median observation time was approximately 5 years
measure: Final Analysis: Time to New Chronic Lymphocytic Leukemia (CLL) Treatment
timeFrame: Median observation time was approximately 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Uab Comprehensive Cancer Center
state: Alabama
city: Fountain Valley
country: United States
facility: Pacific Coast Hematology/Oncology Medical Group
state: California
city: Fresno
country: United States
facility: California Cancer Center Woodward Park; Community Medical Centers
state: California
city: Chicago
country: United States
facility: Rush-Presbyterian St. Luke'S Medical Center
state: Illinois
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Hershey
country: United States
facility: Milton S. Hershey Medical Center; Penn State Cancer Inst.
state: Pennsylvania
city: Sydney
country: Australia
facility: Concord Repatriation General Hospital; Haematology
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Hospital; Division of Cancer Services
state: Queensland
city: Frankston
country: Australia
facility: Frankston Hospital; Oncology/Haematology
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Institute; Medical Oncology
state: Victoria
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Edmonton
country: Canada
facility: Uni of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: St. John's
country: Canada
facility: Health Science Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: QEII HSC; Oncology
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Juravinski Cancer Centre; Hematology
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Regional Hospital - General Campus; Division of Hematology, Box 704
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network; Princess Margaret Hospital; Medical Oncology Dept
state: Ontario
city: Montreal
country: Canada
facility: Mcgill University - Royal Victoria Hospital; Oncology
state: Quebec
city: København Ø
country: Denmark
facility: Righospitalet, Hæmatologisk Klinik
city: Århus
country: Denmark
facility: Aarhus Universitetshospital, Hæmatologisk Afdeling R
city: Bobigny
country: France
facility: Hopital Avicenne; Hematologie Biologique
city: Caen
country: France
facility: Hopital Clemenceau; Hematologie Clinique
city: Clermont Ferrand
country: France
facility: Chu Estaing; Hematologie Clinique Adultes
city: Creteil
country: France
facility: Hopital Henri Mondor; Hematologie Clinique
city: Le Mans
country: France
facility: Clinique Victor Hugo; Chimiotherapie
city: Lille
country: France
facility: Hopital Claude Huriez; Hematologie
city: Lyon
country: France
facility: Hopital Edouard Herriot; Bat.E-Hematologie
city: Lyon
country: France
facility: Centre Leon Berard; Departement Oncologie Medicale
city: Marseille
country: France
facility: Institut J Paolii Calmettes; Onco Hematologie 1
city: Montpellier
country: France
facility: Hôpital Lapeyronie; Hématologie Oncologie Médicale
city: Nantes
country: France
facility: Hopital Hotel Dieu Et Hme;Hopital De Jour
city: Paris
country: France
facility: Hotel Dieu; Hematologie- Oncologie
city: Paris
country: France
facility: Inserm Cic 9504
city: Paris
country: France
facility: Hopital Pitie Salpetriere; Hematologie Clinique
city: Pierre Benite
country: France
facility: Ch Lyon Sud; Hemato Secteur Jules Courmont
city: Poitiers
country: France
facility: Chu La Miletrie; Hdj Cons Hemato Cancerologie
city: Rouen
country: France
facility: Centre Henri Becquerel; Hematologie
city: Tours
country: France
facility: Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
city: Vandoeuvre Les Nancy
country: France
facility: Hopitaux De Brabois; Hematologie Medecine Interne
city: Budapest
country: Hungary
facility: Szent Laszlo Hospital; Hematology Dept
city: Budapest
country: Hungary
facility: National Institute of Oncology, A Dept of Internal Medicine
city: Budapest
country: Hungary
facility: Országos Gyógyintézeti Központ; Haematologiai Osztaly
city: Debrecen
country: Hungary
facility: Uni of Debrecen; 2Nd Clinic of Internal Medicine
city: Debrecen
country: Hungary
facility: University of Debrecen Medical and Health Science Center, Institute of Internal Medicine, Hematology
city: Pecs
country: Hungary
facility: Uni of Pecs; Dept of Internal Medicine
city: Szeged
country: Hungary
facility: University of Szeged, II Dept of Internal Medicine
city: Napoli
country: Italy
facility: A.O. Universitaria Federico II Di Napoli; Oncologia Ed Endocrinologia Clinica
state: Campania
city: Bologna
country: Italy
facility: A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
state: Emilia-Romagna
city: Roma
country: Italy
facility: Ospedale S. Eugenio; Divisione Di Ematologia
state: Lazio
city: Roma
country: Italy
facility: Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo
state: Lazio
city: Roma
country: Italy
facility: Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
state: Lazio
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
state: Lombardia
city: Pavia
country: Italy
facility: Irccs Policlinico San Matteo; Divisione Di Ematologia
state: Lombardia
city: Bari
country: Italy
facility: Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica
state: Puglia
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo
state: Puglia
city: Vicenza
country: Italy
facility: Ospedale Di Vicenza; Nefrologia, Ematologia
state: Veneto
city: Amersfoort
country: Netherlands
facility: Meander Mc, Locatie Lichtenberg; Dept of Lung Diseases
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum Universiteit Amsterdam
city: Den Haag
country: Netherlands
facility: Leyenburg Ziekenhuis; Haematology
city: Rotterdam
country: Netherlands
facility: Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology
city: Auckland
country: New Zealand
facility: Auckland city hospital; Auckland Regional Cancer Centre and Blood Service
city: Christchurch
country: New Zealand
facility: Christchurch Hospital; Canterbury Health Laboratories
city: Wellington
country: New Zealand
facility: Wellington Hospital; Regional Oncology Unit
city: Bergen
country: Norway
facility: Haukeland Universitetshospital; Medicine Dept
city: Oslo
country: Norway
facility: Rikshospitalet Uni Hospital
city: Lodz
country: Poland
facility: Medical University School; Dept. of Haematology
city: Lublin
country: Poland
facility: Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
city: Poznan
country: Poland
facility: Akademii Medycznej W; Klinika Hematologii
city: Warszawa
country: Poland
facility: Klin. Chorob Wewnetrznych I Hemat. Z Osrodkiem Transplant. Szpiku
city: Warszawa
country: Poland
facility: Instytut Hematologii I Transfuzjologii; Klinika Chorob Wewnetrznych I Hematologii
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny; Haematology Dept.
city: Bucharest
country: Romania
facility: Fundeni Clinical Inst. ; Hematology Dept
city: Bucuresti
country: Romania
facility: Spitalul Clinic Coltea; Clinica de Hematologie
city: Targu-mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie
city: Timisoara
country: Romania
facility: Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie
city: Moscow
country: Russian Federation
facility: N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
city: Moscow
country: Russian Federation
facility: Haematology Research Center; Haematology
city: Moscow
country: Russian Federation
facility: City Clinical Botkin's Hospital; City Hematological Center
city: Obninsk
country: Russian Federation
facility: Medical Radiological Research Centre Rams; Dept. of Radiotherapy & Chemotherapy of Hemoblastosis
city: Samara
country: Russian Federation
facility: Regional Clinical Hospital N.A. Kalinin; Hematology Dept
city: St Petersburg
country: Russian Federation
facility: Research Inst. Hematology /Blood Transfusion ; Hemablastosis, Supression Hemopoesis & B M Transplant
city: St Petersburg
country: Russian Federation
facility: Regional Clinical Hospital; Hematology Dept. #2 For B M Transplantation & High Dose Chemo.
city: St Petersburg
country: Russian Federation
facility: Pavlov State Medical Uni ; Bone Marrow Transplantation Clinic
city: St Petersburg
country: Russian Federation
facility: S.-Peterburg Pavlov State Medical University ; Haematology
city: St Petersburg
country: Russian Federation
facility: State Medical Inst. Municipal Hospital #31; Oncology & Hematology Dept. With the Usechemo. in Adult
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa; Servicio de Hematologia
city: Madrid
country: Spain
facility: Hospital Univ. 12 de Octubre; Servicio de Hematologia
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Hematologia
city: Huddinge
country: Sweden
facility: Karolinska Inst. , Huddinge Uni Hospital; Depart. of Hematology
city: Linkoeping
country: Sweden
facility: Universitetssjukhuset i Linköping, Hematologkliniken
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth General Hospital; Haematology
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital; Haematology
city: Glasgow
country: United Kingdom
facility: Stobhill Hospital; Dept of Haematology
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary; Medicine
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary; Dept of Haematology
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Uni Hospital; Haematology
city: London
country: United Kingdom
facility: St. Bartholomew'S Hospital; Dept of Medical Oncology
city: London
country: United Kingdom
facility: King'S College Hospital; Haematology
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital; Academic Dept of Haematology
city: Wakefield
country: United Kingdom
facility: Pinderfields General Hospital; Dept of Haematology
Study officials:
References:
citation: Weisser M, Yeh RF, Duchateau-Nguyen G, Palermo G, Nguyen TQ, Shi X, Stinson SY, Yu N, Dufour A, Robak T, Salogub GN, Dmoszynska A, Solal-Celigny P, Warzocha K, Loscertales J, Catalano J, Larratt L, Rossiev VA, Bence-Bruckler I, Geisler CH, Montillo M, Fischer K, Fink AM, Hallek M, Bloehdorn J, Busch R, Benner A, Dohner H, Valente N, Wenger MK, Stilgenbauer S, Dornan D. PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia. Blood. 2014 Jul 17;124(3):420-5. doi: 10.1182/blood-2013-12-538975. Epub 2014 Jun 10.
citation: Dufour A, Palermo G, Zellmeier E, Mellert G, Duchateau-Nguyen G, Schneider S, Benthaus T, Kakadia PM, Spiekermann K, Hiddemann W, Braess J, Truong S, Patten N, Wu L, Lohmann S, Dornan D, GuhaThakurta D, Yeh RF, Salogub G, Solal-Celigny P, Dmoszynska A, Robak T, Montillo M, Catalano J, Geisler CH, Weisser M, Bohlander SK. Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients. Blood. 2013 May 2;121(18):3650-7. doi: 10.1182/blood-2012-10-458695. Epub 2013 Mar 22.