FCR Versus FC Alone in the Treatment of Chronic Lymphocytic Leukemia (CLL) in Relapsed Patients
|
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. |
| ClinicalTrials.gov Identifier: NCT00090051 |
|
Recruitment Status
:
Completed
First Posted
: August 25, 2004
Results First Posted
: January 23, 2012
Last Update Posted
: August 1, 2017
|
Sponsor:
Hoffmann-La Roche
Collaborators:
Biogen
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Lymphocytic Leukemia | Drug: Rituximab Drug: Fludarabine Phosphate Drug: Cyclophosphamide | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 552 participants |
| 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 |
| Actual Study Start Date : | July 31, 2003 |
| Actual Primary Completion Date : | July 23, 2008 |
| Actual Study Completion Date : | May 31, 2012 |
Resource links provided by the National Library of Medicine
Genetic and Rare Diseases Information Center resources:
Chronic Lymphocytic Leukemia
Leukemia, B-cell, Chronic
U.S. FDA Resources
| Arm | Intervention/treatment |
|---|---|
| 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
|
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.
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| 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
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.
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 Posted: | August 25, 2004 Key Record Dates |
| 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 |