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FCR Versus FC Alone in the Treatment of Chronic Lymphocytic Leukemia (CLL) in Relapsed Patients

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00090051
First Posted: August 25, 2004
Last Update Posted: August 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Biogen
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
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.

Condition Intervention Phase
Chronic Lymphocytic Leukemia Drug: Rituximab Drug: Fludarabine Phosphate Drug: Cyclophosphamide Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC) [ Time Frame: 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.

  • Number of Participants With Progression-free Survival (PFS) Events Assessed by the Independent Review Committee (IRC) [ Time Frame: 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.

  • Final Analysis: Time to Progression-Free Survival Event [ Time Frame: 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:
  • Overall Survival (OS) [ Time Frame: 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.

  • Number of Participants With Overall Survival (OS) Events [ Time Frame: 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.

  • Event-free Survival (EFS) [ Time Frame: 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.

  • Number of Participants With Event-free Survival (EFS) Events [ Time Frame: 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.

  • Disease-free Survival (DFS) [ Time Frame: 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.

  • Number of Participants With Disease-free Survival (DFS) Events [ Time Frame: 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 Overall Survival Event [ Time Frame: 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 [ Time Frame: 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.

  • Final Analysis: Percentage of Participants With Complete Response [ Time Frame: Median observation time was approximately 5 years ]
    Complete response was defined as the disappearance of all signs of cancer in response to treatment.

  • Final Analysis: Time to Disease-Free Survival Event [ Time Frame: 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.

  • Final Analysis: Duration of Response [ Time Frame: 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.

  • Final Analysis: Time to New Chronic Lymphocytic Leukemia (CLL) Treatment [ Time Frame: 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.


Enrollment: 552
Actual Study Start Date: July 31, 2003
Study Completion Date: May 31, 2012
Primary Completion Date: July 23, 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fludarabine+Cyclophosphamide (FC) Drug: Fludarabine Phosphate
Intravenous repeating dose
Drug: Cyclophosphamide
Intravenous repeating dose
Experimental: Fludarabine+Cyclophosphamide+Rituximab (FCR) Drug: Rituximab
Intravenous repeating dose
Drug: Fludarabine Phosphate
Intravenous repeating dose
Drug: Cyclophosphamide
Intravenous repeating dose

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00090051


  Hide Study Locations
Locations
United States, Alabama
Uab Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-3300
United States, California
Pacific Coast Hematology/Oncology Medical Group
Fountain Valley, California, United States, 92708
California Cancer Center Woodward Park; Community Medical Centers
Fresno, California, United States, 93720
United States, Illinois
Rush-Presbyterian St. Luke'S Medical Center
Chicago, Illinois, United States, 60612
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Milton S. Hershey Medical Center; Penn State Cancer Inst.
Hershey, Pennsylvania, United States, 17033
Australia, New South Wales
Concord Repatriation General Hospital; Haematology
Sydney, New South Wales, Australia, 2139
Australia, Queensland
Mater Hospital; Division of Cancer Services
Brisbane, Queensland, Australia, 4101
Australia, Victoria
Frankston Hospital; Oncology/Haematology
Frankston, Victoria, Australia, 3199
Peter Maccallum Cancer Institute; Medical Oncology
Melbourne, Victoria, Australia, 3000
Belgium
ZNA Stuivenberg
Antwerpen, Belgium, 2060
Institut Jules Bordet
Bruxelles, Belgium, 1000
UZ Leuven Gasthuisberg
Leuven, Belgium, 3000
Canada, Alberta
Uni of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2R7
Canada, British Columbia
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Newfoundland and Labrador
Health Science Centre
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Nova Scotia
QEII HSC; Oncology
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Hamilton Health Sciences - Juravinski Cancer Centre; Hematology
Hamilton, Ontario, Canada, L8V 5C2
The Ottawa Regional Hospital - General Campus; Division of Hematology, Box 704
Ottawa, Ontario, Canada, K1H 1C4
Sunnybrook Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Mcgill University - Royal Victoria Hospital; Oncology
Montreal, Quebec, Canada, H3A 1A1
Denmark
Righospitalet, Hæmatologisk Klinik
København Ø, Denmark, 2100
Aarhus Universitetshospital, Hæmatologisk Afdeling R
Århus, Denmark, 8000
France
Hopital Avicenne; Hematologie Biologique
Bobigny, France, 93009
Hopital Clemenceau; Hematologie Clinique
Caen, France, 14033
Chu Estaing; Hematologie Clinique Adultes
Clermont Ferrand, France, 63003
Hopital Henri Mondor; Hematologie Clinique
Creteil, France, 94010
Clinique Victor Hugo; Chimiotherapie
Le Mans, France, 72015
Hopital Claude Huriez; Hematologie
Lille, France, 59037
Hopital Edouard Herriot; Bat.E-Hematologie
Lyon, France, 69003
Centre Leon Berard; Departement Oncologie Medicale
Lyon, France, 69373
Institut J Paolii Calmettes; Onco Hematologie 1
Marseille, France, 13273
Hôpital Lapeyronie; Hématologie Oncologie Médicale
Montpellier, France, 34295
Hopital Hotel Dieu Et Hme;Hopital De Jour
Nantes, France, 44093
Hotel Dieu; Hematologie- Oncologie
Paris, France, 75181
Inserm Cic 9504
Paris, France, 75475
Hopital Pitie Salpetriere; Hematologie Clinique
Paris, France, 75651
Ch Lyon Sud; Hemato Secteur Jules Courmont
Pierre Benite, France, 69495
Chu La Miletrie; Hdj Cons Hemato Cancerologie
Poitiers, France, 86021
Centre Henri Becquerel; Hematologie
Rouen, France, 76038
Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
Tours, France, 37044
Hopitaux De Brabois; Hematologie Medecine Interne
Vandoeuvre Les Nancy, France, 54511
Hungary
Szent Laszlo Hospital; Hematology Dept
Budapest, Hungary, 1097
National Institute of Oncology, A Dept of Internal Medicine
Budapest, Hungary, 1122
Országos Gyógyintézeti Központ; Haematologiai Osztaly
Budapest, Hungary, 1135
Uni of Debrecen; 2Nd Clinic of Internal Medicine
Debrecen, Hungary, 4004
University of Debrecen Medical and Health Science Center, Institute of Internal Medicine, Hematology
Debrecen, Hungary, 4032
Uni of Pecs; Dept of Internal Medicine
Pecs, Hungary, 7624
University of Szeged, II Dept of Internal Medicine
Szeged, Hungary, 6720
Italy
A.O. Universitaria Federico II Di Napoli; Oncologia Ed Endocrinologia Clinica
Napoli, Campania, Italy, 80131
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
Bologna, Emilia-Romagna, Italy, 40138
Ospedale S. Eugenio; Divisione Di Ematologia
Roma, Lazio, Italy, 00144
Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo
Roma, Lazio, Italy, 00152
Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
Roma, Lazio, Italy, 00161
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
Milano, Lombardia, Italy, 20162
Irccs Policlinico San Matteo; Divisione Di Ematologia
Pavia, Lombardia, Italy, 27100
Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica
Bari, Puglia, Italy, 70124
IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo
San Giovanni Rotondo, Puglia, Italy, 71013
Ospedale Di Vicenza; Nefrologia, Ematologia
Vicenza, Veneto, Italy, 36100
Netherlands
Meander Mc, Locatie Lichtenberg; Dept of Lung Diseases
Amersfoort, Netherlands, 3818 ES
Academisch Medisch Centrum Universiteit Amsterdam
Amsterdam, Netherlands, 1105 AZ
Leyenburg Ziekenhuis; Haematology
Den Haag, Netherlands, 2545 CG
Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology
Rotterdam, Netherlands, 3075 EA
New Zealand
Auckland city hospital; Auckland Regional Cancer Centre and Blood Service
Auckland, New Zealand, 1023
Christchurch Hospital; Canterbury Health Laboratories
Christchurch, New Zealand
Wellington Hospital; Regional Oncology Unit
Wellington, New Zealand, 6002
Norway
Haukeland Universitetshospital; Medicine Dept
Bergen, Norway, 5021
Rikshospitalet Uni Hospital
Oslo, Norway, 0027
Poland
Medical University School; Dept. of Haematology
Lodz, Poland, 93-510
Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
Lublin, Poland, 20-081
Akademii Medycznej W; Klinika Hematologii
Poznan, Poland, 02-097
Klin. Chorob Wewnetrznych I Hemat. Z Osrodkiem Transplant. Szpiku
Warszawa, Poland, 00-909
Instytut Hematologii I Transfuzjologii; Klinika Chorob Wewnetrznych I Hematologii
Warszawa, Poland, 00-957
Samodzielny Publiczny Centralny Szpital Kliniczny; Haematology Dept.
Warszawa, Poland, 02-097
Romania
Fundeni Clinical Inst. ; Hematology Dept
Bucharest, Romania, 022328
Spitalul Clinic Coltea; Clinica de Hematologie
Bucuresti, Romania, 030171
Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie
Targu-mures, Romania, 540136
Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie
Timisoara, Romania, 300079
Russian Federation
N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
Moscow, Russian Federation, 115478
Haematology Research Center; Haematology
Moscow, Russian Federation, 125167
City Clinical Botkin's Hospital; City Hematological Center
Moscow, Russian Federation, 125284
Medical Radiological Research Centre Rams; Dept. of Radiotherapy & Chemotherapy of Hemoblastosis
Obninsk, Russian Federation, 249036
Regional Clinical Hospital N.A. Kalinin; Hematology Dept
Samara, Russian Federation, 443095
Research Inst. Hematology /Blood Transfusion ; Hemablastosis, Supression Hemopoesis & B M Transplant
St Petersburg, Russian Federation, 193024
Regional Clinical Hospital; Hematology Dept. #2 For B M Transplantation & High Dose Chemo.
St Petersburg, Russian Federation, 194291
Pavlov State Medical Uni ; Bone Marrow Transplantation Clinic
St Petersburg, Russian Federation, 197022
S.-Peterburg Pavlov State Medical University ; Haematology
St Petersburg, Russian Federation, 197022
State Medical Inst. Municipal Hospital #31; Oncology & Hematology Dept. With the Usechemo. in Adult
St Petersburg, Russian Federation, 197110
Spain
Hospital Universitario de la Princesa; Servicio de Hematologia
Madrid, Spain, 28006
Hospital Univ. 12 de Octubre; Servicio de Hematologia
Madrid, Spain, 28041
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
Salamanca, Spain, 37007
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Valencia, Spain, 46010
Hospital Universitario Miguel Servet; Servicio Hematologia
Zaragoza, Spain, 50009
Sweden
Karolinska Inst. , Huddinge Uni Hospital; Depart. of Hematology
Huddinge, Sweden, 14186
Universitetssjukhuset i Linköping, Hematologkliniken
Linkoeping, Sweden, 581 85
United Kingdom
Royal Bournemouth General Hospital; Haematology
Bournemouth, United Kingdom, BH7 7DW
Addenbrookes Hospital; Haematology
Cambridge, United Kingdom, CB2 0QQ
Stobhill Hospital; Dept of Haematology
Glasgow, United Kingdom, G83 8NG
Leeds General Infirmary; Medicine
Leeds, United Kingdom, LS1 3EX
Leicester Royal Infirmary; Dept of Haematology
Leicester, United Kingdom, LE1 5WW
Royal Liverpool Uni Hospital; Haematology
Liverpool, United Kingdom, L7 8XP
St. Bartholomew'S Hospital; Dept of Medical Oncology
London, United Kingdom, EC1A 7BE
King'S College Hospital; Haematology
London, United Kingdom, SE5 9RS
Royal Marsden Hospital; Academic Dept of Haematology
Sutton, United Kingdom, SW3 6JJ
Pinderfields General Hospital; Dept of Haematology
Wakefield, United Kingdom, WF1 4DG
Sponsors and Collaborators
Hoffmann-La Roche
Biogen
Genentech, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00090051     History of Changes
Other Study ID Numbers: 102-14
BO17072
First Submitted: August 23, 2004
First Posted: August 25, 2004
Results First Submitted: December 22, 2009
Results First Posted: January 23, 2012
Last Update Posted: August 1, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Rituximab
Leukemia
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites