FCR Versus FC Alone in the Treatment of Chronic Lymphocytic Leukemia (CLL) in Relapsed Patients
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT00090051
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 552
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fludarabine+Cyclophosphamide+Rituximab (FCR) Rituximab - Fludarabine+Cyclophosphamide+Rituximab (FCR) Fludarabine Phosphate - Fludarabine+Cyclophosphamide (FC) Fludarabine Phosphate - Fludarabine+Cyclophosphamide+Rituximab (FCR) Cyclophosphamide - Fludarabine+Cyclophosphamide (FC) Cyclophosphamide -
- Primary Outcome Measures
Name Time Method Number of Participants With Progression-free Survival (PFS) Events Assessed by the Independent Review Committee (IRC) Mean observation time at time of analysis was approximately 26 months Progression-free survival as assessed by the IRC was defined as the time between randomization and the date of first documented disease progression, relapse after response, or death from any cause (PFS events), whichever came first. Patients without a PFS event were censored at their last tumor assessment date.
Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC) Mean observation time at time of analysis was approximately 26 months Progression-free survival as assessed by the IRC was defined as the time between randomization and the date of first documented disease progression, relapse after response, or death from any cause, whichever came first. Patients without a PFS event were censored at their last tumor assessment date.
Final Analysis: Time to Progression-Free Survival Event Median observation time was approximately 5 years Time to progression-free survival (PFS) event was defined as the time between randomization and the date of first documented PFS event: disease progression, relapse or death by any cause, whichever came first.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Mean observation time at time of analysis was approximately 26 months Overall survival was determined from the date of randomization to the date of death irrespective of cause. Patients who had not died at the time of the final analysis (clinical data cut-off) were censored at the date of the last contact.
Final Analysis: Duration of Response Median observation time was approximately 5 years Duration of response was defined as the time between the date of the earliest qualifying response and the date of disease progression or death due to any cause.
Number of Participants With Event-free Survival (EFS) Events Mean observation time at time of analysis was approximately 26 months Event free survival was measured from the day of randomization to the date of first documented Progressive Disease (PD), relapse after response, start of a new treatment or death from any cause (EFS events). Patients without an EFS event were censored at their last tumor assessment date.
Final Analysis: Percentage of Participants With Complete Response Median observation time was approximately 5 years Complete response was defined as the disappearance of all signs of cancer in response to treatment.
Number of Participants With Overall Survival (OS) Events Mean observation time at time of analysis was approximately 26 months Overall survival was determined from the date of randomization to the date of death (OS event) irrespective of cause. Patients who had not died at the time of the final analysis (clinical data cut-off) were censored at the date of the last contact.
Number of Participants With Disease-free Survival (DFS) Events Mean observation time at time of analysis was approximately 26 months Disease free survival was defined for all patients with a best overall response (BOR) of Complete Response (CR) and measured the time from first documented CR in a sequence of consecutive CRs until documented disease progression, relapse or death from any cause (DFS events). Patients without a DFS event at the time of the analysis (clinical data cut-off) were censored at their last tumor assessment date.
Final Analysis: Time to Disease-Free Survival Event Median observation time was approximately 5 years Time to disease-free survival (DFS) event was defined as the time from first documented response until the first documented DFS event: disease progression, relapse or death from any cause.
Disease-free Survival (DFS) Mean observation time at time of analysis was approximately 26 months Disease free survival was defined for all patients with a best overall response (BOR) of Complete Response (CR) and measured the time from first documented CR in a sequence of consecutive CRs until documented disease progression, relapse or death from any cause. Patients without a DFS event at the time of the analysis (clinical data cut-off) were censored at their last tumor assessment date.
Final Analysis: Time to Overall Survival Event Median observation time was approximately 5 years Overall survival (OS) was determined from the date of randomization to the date of death (OS event) irrespective of cause.
Final Analysis: Time to Event-Free Survival Event Median observation time was approximately 5 years Event free survival (EFS) was defined as the time from the day of randomization to the date of first EFS event: documented disease progression, relapse after response, start of a new treatment or death from any cause.
Event-free Survival (EFS) Mean observation time at time of analysis was approximately 26 months Event free survival was measured from the day of randomization to the date of first documented PD, relapse after response, start of a new treatment or death from any cause. Patients without an EFS event were censored at their last tumor assessment date.
Final Analysis: Time to New Chronic Lymphocytic Leukemia (CLL) Treatment Median observation time was approximately 5 years Time to new CCL treatment was defined as the time from randomization to the first day of new treatment for CCL or death.
Trial Locations
- Locations (106)
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
🇪🇸Salamanca, Spain
Rush-Presbyterian St. Luke'S Medical Center
🇺🇸Chicago, Illinois, United States
Sunnybrook Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
🇨🇦Toronto, Ontario, Canada
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
🇮🇹Roma, Lazio, Italy
Research Inst. Hematology /Blood Transfusion ; Hemablastosis, Supression Hemopoesis & B M Transplant
🇷🇺St Petersburg, Russian Federation
Szent Laszlo Hospital; Hematology Dept
🇭🇺Budapest, Hungary
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
Meander Mc, Locatie Lichtenberg; Dept of Lung Diseases
🇳🇱Amersfoort, Netherlands
Regional Clinical Hospital N.A. Kalinin; Hematology Dept
🇷🇺Samara, Russian Federation
National Institute of Oncology, A Dept of Internal Medicine
🇭🇺Budapest, Hungary
Mcgill University - Royal Victoria Hospital; Oncology
🇨🇦Montreal, Quebec, Canada
QEII HSC; Oncology
🇨🇦Halifax, Nova Scotia, Canada
Uni of Debrecen; 2Nd Clinic of Internal Medicine
🇭🇺Debrecen, Hungary
Uni of Pecs; Dept of Internal Medicine
🇭🇺Pecs, Hungary
Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie
🇷🇴Timisoara, Romania
Medical University School; Dept. of Haematology
🇵🇱Lodz, Poland
Medical Radiological Research Centre Rams; Dept. of Radiotherapy & Chemotherapy of Hemoblastosis
🇷🇺Obninsk, Russian Federation
City Clinical Botkin's Hospital; City Hematological Center
🇷🇺Moscow, Russian Federation
Regional Clinical Hospital; Hematology Dept. #2 For B M Transplantation & High Dose Chemo.
🇷🇺St Petersburg, Russian Federation
Uab Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Pacific Coast Hematology/Oncology Medical Group
🇺🇸Fountain Valley, California, United States
California Cancer Center Woodward Park; Community Medical Centers
🇺🇸Fresno, California, United States
Mater Hospital; Division of Cancer Services
🇦🇺Brisbane, Queensland, Australia
Milton S. Hershey Medical Center; Penn State Cancer Inst.
🇺🇸Hershey, Pennsylvania, United States
Frankston Hospital; Oncology/Haematology
🇦🇺Frankston, Victoria, Australia
Peter Maccallum Cancer Institute; Medical Oncology
🇦🇺Melbourne, Victoria, Australia
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
Uni of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
BCCA-Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Health Science Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Hamilton Health Sciences - Juravinski Cancer Centre; Hematology
🇨🇦Hamilton, Ontario, Canada
The Ottawa Regional Hospital - General Campus; Division of Hematology, Box 704
🇨🇦Ottawa, Ontario, Canada
Righospitalet, Hæmatologisk Klinik
🇩🇰København Ø, Denmark
Aarhus Universitetshospital, Hæmatologisk Afdeling R
🇩🇰Århus, Denmark
Hopital Avicenne; Hematologie Biologique
🇫🇷Bobigny, France
Hopital Henri Mondor; Hematologie Clinique
🇫🇷Creteil, France
Chu Estaing; Hematologie Clinique Adultes
🇫🇷Clermont Ferrand, France
Hopital Clemenceau; Hematologie Clinique
🇫🇷Caen, France
Clinique Victor Hugo; Chimiotherapie
🇫🇷Le Mans, France
Hotel Dieu; Hematologie- Oncologie
🇫🇷Paris, France
Hopital Edouard Herriot; Bat.E-Hematologie
🇫🇷Lyon, France
Centre Leon Berard; Departement Oncologie Medicale
🇫🇷Lyon, France
Hopital Claude Huriez; Hematologie
🇫🇷Lille, France
Institut J Paolii Calmettes; Onco Hematologie 1
🇫🇷Marseille, France
Hôpital Lapeyronie; Hématologie Oncologie Médicale
🇫🇷Montpellier, France
Inserm Cic 9504
🇫🇷Paris, France
Hopital Hotel Dieu Et Hme;Hopital De Jour
🇫🇷Nantes, France
Ch Lyon Sud; Hemato Secteur Jules Courmont
🇫🇷Pierre Benite, France
Hopital Pitie Salpetriere; Hematologie Clinique
🇫🇷Paris, France
Chu La Miletrie; Hdj Cons Hemato Cancerologie
🇫🇷Poitiers, France
Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
🇫🇷Tours, France
Hopitaux De Brabois; Hematologie Medecine Interne
🇫🇷Vandoeuvre Les Nancy, France
Centre Henri Becquerel; Hematologie
🇫🇷Rouen, France
University of Szeged, II Dept of Internal Medicine
🇭🇺Szeged, Hungary
University of Debrecen Medical and Health Science Center, Institute of Internal Medicine, Hematology
🇭🇺Debrecen, Hungary
Országos Gyógyintézeti Központ; Haematologiai Osztaly
🇭🇺Budapest, Hungary
Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo
🇮🇹Roma, Lazio, Italy
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
🇮🇹Bologna, Emilia-Romagna, Italy
Ospedale S. Eugenio; Divisione Di Ematologia
🇮🇹Roma, Lazio, Italy
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
🇮🇹Milano, Lombardia, Italy
Irccs Policlinico San Matteo; Divisione Di Ematologia
🇮🇹Pavia, Lombardia, Italy
IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo
🇮🇹San Giovanni Rotondo, Puglia, Italy
Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica
🇮🇹Bari, Puglia, Italy
Ospedale Di Vicenza; Nefrologia, Ematologia
🇮🇹Vicenza, Veneto, Italy
Academisch Medisch Centrum Universiteit Amsterdam
🇳🇱Amsterdam, Netherlands
Leyenburg Ziekenhuis; Haematology
🇳🇱Den Haag, Netherlands
Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology
🇳🇱Rotterdam, Netherlands
Auckland city hospital; Auckland Regional Cancer Centre and Blood Service
🇳🇿Auckland, New Zealand
Wellington Hospital; Regional Oncology Unit
🇳🇿Wellington, New Zealand
Christchurch Hospital; Canterbury Health Laboratories
🇳🇿Christchurch, New Zealand
Haukeland Universitetshospital; Medicine Dept
🇳🇴Bergen, Norway
Rikshospitalet Uni Hospital
🇳🇴Oslo, Norway
Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
🇵🇱Lublin, Poland
Akademii Medycznej W; Klinika Hematologii
🇵🇱Poznan, Poland
Klin. Chorob Wewnetrznych I Hemat. Z Osrodkiem Transplant. Szpiku
🇵🇱Warszawa, Poland
Instytut Hematologii I Transfuzjologii; Klinika Chorob Wewnetrznych I Hematologii
🇵🇱Warszawa, Poland
Fundeni Clinical Inst. ; Hematology Dept
🇷🇴Bucharest, Romania
Samodzielny Publiczny Centralny Szpital Kliniczny; Haematology Dept.
🇵🇱Warszawa, Poland
Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie
🇷🇴Targu-mures, Romania
Spitalul Clinic Coltea; Clinica de Hematologie
🇷🇴Bucuresti, Romania
N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
🇷🇺Moscow, Russian Federation
Haematology Research Center; Haematology
🇷🇺Moscow, Russian Federation
Hospital Universitario de la Princesa; Servicio de Hematologia
🇪🇸Madrid, Spain
S.-Peterburg Pavlov State Medical University ; Haematology
🇷🇺St Petersburg, Russian Federation
Pavlov State Medical Uni ; Bone Marrow Transplantation Clinic
🇷🇺St Petersburg, Russian Federation
State Medical Inst. Municipal Hospital #31; Oncology & Hematology Dept. With the Usechemo. in Adult
🇷🇺St Petersburg, Russian Federation
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
🇪🇸Valencia, Spain
Karolinska Inst. , Huddinge Uni Hospital; Depart. of Hematology
🇸🇪Huddinge, Sweden
Hospital Universitario Miguel Servet; Servicio Hematologia
🇪🇸Zaragoza, Spain
Universitetssjukhuset i Linköping, Hematologkliniken
🇸🇪Linkoeping, Sweden
Royal Bournemouth General Hospital; Haematology
🇬🇧Bournemouth, United Kingdom
Addenbrookes Hospital; Haematology
🇬🇧Cambridge, United Kingdom
Stobhill Hospital; Dept of Haematology
🇬🇧Glasgow, United Kingdom
Leicester Royal Infirmary; Dept of Haematology
🇬🇧Leicester, United Kingdom
Leeds General Infirmary; Medicine
🇬🇧Leeds, United Kingdom
Royal Liverpool Uni Hospital; Haematology
🇬🇧Liverpool, United Kingdom
King'S College Hospital; Haematology
🇬🇧London, United Kingdom
St. Bartholomew'S Hospital; Dept of Medical Oncology
🇬🇧London, United Kingdom
Royal Marsden Hospital; Academic Dept of Haematology
🇬🇧Sutton, United Kingdom
Pinderfields General Hospital; Dept of Haematology
🇬🇧Wakefield, United Kingdom
Hospital Univ. 12 de Octubre; Servicio de Hematologia
🇪🇸Madrid, Spain
Concord Repatriation General Hospital; Haematology
🇦🇺Sydney, New South Wales, Australia
A.O. Universitaria Federico II Di Napoli; Oncologia Ed Endocrinologia Clinica
🇮🇹Napoli, Campania, Italy