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

NCT00090051 | Completed Phase 3 Results DMC

• 2 other identifiers: 102-14BO17072
• Study Type: interventional
• Target: 552
• Locations: 17 countries
• Sites: 106

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.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (3)

• Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC)

  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.

  Mean observation time at time of analysis was approximately 26 months

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

  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.

  Mean observation time at time of analysis was approximately 26 months

• Final Analysis: Time to Progression-Free Survival Event

  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.

  Median observation time was approximately 5 years

Secondary Outcomes (12)

• Overall Survival (OS)

  Mean observation time at time of analysis was approximately 26 months

• Number of Participants With Overall Survival (OS) Events

  Mean observation time at time of analysis was approximately 26 months

• Event-free Survival (EFS)

  Mean observation time at time of analysis was approximately 26 months

• Number of Participants With Event-free Survival (EFS) Events

  Mean observation time at time of analysis was approximately 26 months

• Disease-free Survival (DFS)

  Mean observation time at time of analysis was approximately 26 months

Study Arms (2)

Fludarabine+Cyclophosphamide (FC)

ACTIVE COMPARATOR

Drug: Fludarabine Phosphate; Drug: Cyclophosphamide

Fludarabine+Cyclophosphamide+Rituximab (FCR)

EXPERIMENTAL

Drug: Rituximab; Drug: Fludarabine Phosphate; Drug: Cyclophosphamide

Interventions

Rituximab DRUG

Intravenous repeating dose

Fludarabine+Cyclophosphamide+Rituximab (FCR)

Fludarabine Phosphate DRUG

Intravenous repeating dose

Fludarabine+Cyclophosphamide (FC); Fludarabine+Cyclophosphamide+Rituximab (FCR)

Cyclophosphamide DRUG

Intravenous repeating dose

Fludarabine+Cyclophosphamide (FC); Fludarabine+Cyclophosphamide+Rituximab (FCR)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Biogen: collaborator
• Genentech, Inc.: collaborator

Study Sites (106)

Uab Comprehensive Cancer Center

Birmingham, Alabama, 35294-3300, United States

Location

Pacific Coast Hematology/Oncology Medical Group

Fountain Valley, California, 92708, United States

Location

California Cancer Center Woodward Park; Community Medical Centers

Fresno, California, 93720, United States

Location

Rush-Presbyterian St. Luke'S Medical Center

Chicago, Illinois, 60612, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Milton S. Hershey Medical Center; Penn State Cancer Inst.

Hershey, Pennsylvania, 17033, United States

Location

Concord Repatriation General Hospital; Haematology

Sydney, New South Wales, 2139, Australia

Location

Mater Hospital; Division of Cancer Services

Brisbane, Queensland, 4101, Australia

Location

Frankston Hospital; Oncology/Haematology

Frankston, Victoria, 3199, Australia

Location

Peter Maccallum Cancer Institute; Medical Oncology

Melbourne, Victoria, 3000, Australia

Location

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Uni of Alberta Hospital

Edmonton, Alberta, T6G 2R7, Canada

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Health Science Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

QEII HSC; Oncology

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Hamilton Health Sciences - Juravinski Cancer Centre; Hematology

Hamilton, Ontario, L8V 5C2, Canada

Location

The Ottawa Regional Hospital - General Campus; Division of Hematology, Box 704

Ottawa, Ontario, K1H 1C4, Canada

Location

Sunnybrook Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

Mcgill University - Royal Victoria Hospital; Oncology

Montreal, Quebec, H3A 1A1, Canada

Location

Aarhus Universitetshospital, Hæmatologisk Afdeling R

Aarhus, 8000, Denmark

Location

Righospitalet, Hæmatologisk Klinik

København Ø, 2100, Denmark

Location

Hopital Avicenne; Hematologie Biologique

Bobigny, 93009, France

Location

Hopital Clemenceau; Hematologie Clinique

Caen, 14033, France

Location

Chu Estaing; Hematologie Clinique Adultes

Clermont-Ferrand, 63003, France

Location

Hopital Henri Mondor; Hematologie Clinique

Créteil, 94010, France

Location

Clinique Victor Hugo; Chimiotherapie

Le Mans, 72015, France

Location

Hopital Claude Huriez; Hematologie

Lille, 59037, France

Location

Hopital Edouard Herriot; Bat.E-Hematologie

Lyon, 69003, France

Location

Centre Leon Berard; Departement Oncologie Medicale

Lyon, 69373, France

Location

Institut J Paolii Calmettes; Onco Hematologie 1

Marseille, 13273, France

Location

Hôpital Lapeyronie; Hématologie Oncologie Médicale

Montpellier, 34295, France

Location

Hopital Hotel Dieu Et Hme;Hopital De Jour

Nantes, 44093, France

Location

Hotel Dieu; Hematologie- Oncologie

Paris, 75181, France

Location

Inserm Cic 9504

Paris, 75475, France

Location

Hopital Pitie Salpetriere; Hematologie Clinique

Paris, 75651, France

Location

Ch Lyon Sud; Hemato Secteur Jules Courmont

Pierre-Bénite, 69495, France

Location

Chu La Miletrie; Hdj Cons Hemato Cancerologie

Poitiers, 86021, France

Location

Centre Henri Becquerel; Hematologie

Rouen, 76038, France

Location

Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie

Tours, 37044, France

Location

Hopitaux De Brabois; Hematologie Medecine Interne

Vandœuvre-lès-Nancy, 54511, France

Location

Szent Laszlo Hospital; Hematology Dept

Budapest, 1097, Hungary

Location

National Institute of Oncology, A Dept of Internal Medicine

Budapest, 1122, Hungary

Location

Országos Gyógyintézeti Központ; Haematologiai Osztaly

Budapest, 1135, Hungary

Location

Uni of Debrecen; 2Nd Clinic of Internal Medicine

Debrecen, 4004, Hungary

Location

University of Debrecen Medical and Health Science Center, Institute of Internal Medicine, Hematology

Debrecen, 4032, Hungary

Location

Uni of Pecs; Dept of Internal Medicine

Pécs, 7624, Hungary

Location

University of Szeged, II Dept of Internal Medicine

Szeged, 6720, Hungary

Location

Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica

Bari, Apulia, 70124, Italy

Location

IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo

San Giovanni Rotondo, Apulia, 71013, Italy

Location

A.O. Universitaria Federico II Di Napoli; Oncologia Ed Endocrinologia Clinica

Napoli, Campania, 80131, Italy

Location

A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna

Bologna, Emilia-Romagna, 40138, Italy

Location

Ospedale S. Eugenio; Divisione Di Ematologia

Rome, Lazio, 00144, Italy

Location

Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo

Rome, Lazio, 00152, Italy

Location

Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA

Rome, Lazio, 00161, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milan, Lombardy, 20162, Italy

Location

Irccs Policlinico San Matteo; Divisione Di Ematologia

Pavia, Lombardy, 27100, Italy

Location

Ospedale Di Vicenza; Nefrologia, Ematologia

Vicenza, Veneto, 36100, Italy

Location

Meander Mc, Locatie Lichtenberg; Dept of Lung Diseases

Amersfoort, 3818 ES, Netherlands

Location

Academisch Medisch Centrum Universiteit Amsterdam

Amsterdam, 1105 AZ, Netherlands

Location

Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology

Rotterdam, 3075 EA, Netherlands

Location

Leyenburg Ziekenhuis; Haematology

The Hague, 2545 CG, Netherlands

Location

Auckland city hospital; Auckland Regional Cancer Centre and Blood Service

Auckland, 1023, New Zealand

Location

Christchurch Hospital; Canterbury Health Laboratories

Christchurch, New Zealand

Location

Wellington Hospital; Regional Oncology Unit

Wellington, 6002, New Zealand

Location

Haukeland Universitetshospital; Medicine Dept

Bergen, 5021, Norway

Location

Rikshospitalet Uni Hospital

Oslo, 0027, Norway

Location

Medical University School; Dept. of Haematology

Lodz, 93-510, Poland

Location

Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie

Lublin, 20-081, Poland

Location

Akademii Medycznej W; Klinika Hematologii

Poznan, 02-097, Poland

Location

Klin. Chorob Wewnetrznych I Hemat. Z Osrodkiem Transplant. Szpiku

Warsaw, 00-909, Poland

Location

Instytut Hematologii I Transfuzjologii; Klinika Chorob Wewnetrznych I Hematologii

Warsaw, 00-957, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny; Haematology Dept.

Warsaw, 02-097, Poland

Location

Fundeni Clinical Inst. ; Hematology Dept

Bucharest, 022328, Romania

Location

Spitalul Clinic Coltea; Clinica de Hematologie

Bucharest, 030171, Romania

Location

Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie

Târgu Mureş, 540136, Romania

Location

Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie

Timișoara, 300079, Romania

Location

N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis

Moscow, 115478, Russia

Location

Haematology Research Center; Haematology

Moscow, 125167, Russia

Location

City Clinical Botkin's Hospital; City Hematological Center

Moscow, 125284, Russia

Location

Medical Radiological Research Centre Rams; Dept. of Radiotherapy & Chemotherapy of Hemoblastosis

Obninsk, 249036, Russia

Location

Research Inst. Hematology /Blood Transfusion ; Hemablastosis, Supression Hemopoesis & B M Transplant

Saint Petersburg, 193024, Russia

Location

Regional Clinical Hospital; Hematology Dept. #2 For B M Transplantation & High Dose Chemo.

Saint Petersburg, 194291, Russia

Location

Pavlov State Medical Uni ; Bone Marrow Transplantation Clinic

Saint Petersburg, 197022, Russia

Location

S.-Peterburg Pavlov State Medical University ; Haematology

Saint Petersburg, 197022, Russia

Location

State Medical Inst. Municipal Hospital #31; Oncology & Hematology Dept. With the Usechemo. in Adult

Saint Petersburg, 197110, Russia

Location

Regional Clinical Hospital N.A. Kalinin; Hematology Dept

Samara, 443095, Russia

Location

Hospital Universitario de la Princesa; Servicio de Hematologia

Madrid, 28006, Spain

Location

Hospital Univ. 12 de Octubre; Servicio de Hematologia

Madrid, 28041, Spain

Location

Hospital Clinico Universitario de Salamanca;Servicio de Hematologia

Salamanca, 37007, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet; Servicio Hematologia

Zaragoza, 50009, Spain

Location

Karolinska Inst. , Huddinge Uni Hospital; Depart. of Hematology

Huddinge, 14186, Sweden

Location

Universitetssjukhuset i Linköping, Hematologkliniken

Linköping, 581 85, Sweden

Location

Royal Bournemouth General Hospital; Haematology

Bournemouth, BH7 7DW, United Kingdom

Location

Addenbrookes Hospital; Haematology

Cambridge, CB2 0QQ, United Kingdom

Location

Stobhill Hospital; Dept of Haematology

Glasgow, G83 8NG, United Kingdom

Location

Leeds General Infirmary; Medicine

Leeds, LS1 3EX, United Kingdom

Location

Leicester Royal Infirmary; Dept of Haematology

Leicester, LE1 5WW, United Kingdom

Location

Royal Liverpool Uni Hospital; Haematology

Liverpool, L7 8XP, United Kingdom

Location

St. Bartholomew'S Hospital; Dept of Medical Oncology

London, EC1A 7BE, United Kingdom

Location

King'S College Hospital; Haematology

London, SE5 9RS, United Kingdom

Location

Royal Marsden Hospital; Academic Dept of Haematology

Sutton, SW3 6JJ, United Kingdom

Location

Pinderfields General Hospital; Dept of Haematology

Wakefield, WF1 4DG, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 24916506 DERIVED

• 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.

  PMID: 23525797 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Rituximab; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

global.clinical_trial_registry@roche.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2004
• First Posted: August 25, 2004
• Study Start: July 31, 2003
• Primary Completion: July 23, 2008
• Study Completion: May 31, 2012
• Last Updated: August 1, 2017
• Results First Posted: January 23, 2012

Record last verified: 2017-07

Locations

IT (10); ES (5); RU (10); SE (2); GB (10); NO (2); FR (19); DK (2); AU (4); RO (4); NL (4); NZ (3); CA (9); HU (7); PL (6); BE (3); US (6)