AzTrials
AzTrials

Chronic Lymphocytic LeukemiaPhase 3NCT00275054

Rituximab, Fludarabine, and Cyclophosphamide or Observation Alone in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia

A Phase 3 study testing Fludarabine, Cyclophosphamide and Rituximab in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 91 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Fludarabine, Cyclophosphamide and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
825 participants
Where
91 sitesin 3 countries
Study dates
Oct 2005to Jun 2015
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Established diagnosis of B-cell chronic lymphocytic leukemia
  • First diagnosis within 12 months before inclusion in study
  • Previously untreated disease
  • Binet stage A disease (Rai stage 0, I, or II)

PATIENT CHARACTERISTICS:

  • Life expectancy > 6 months
  • ECOG performance status 0-2
  • Willingness to accept contraception (if randomized to arm I) for the duration of therapy and 12 months thereafter
  • Negative serum pregnancy test
  • All parameters for risk stratification (lymphocyte doubling time, cytogenetics, unmutated IgVH, and serum thymidine kinase level > 10) present

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiotherapy, or antibody treatment
  • No other concurrent chemotherapy

Trial locations and contacts

91 sites in 3 countries.

91 sites in 3 countries

Germany65 sites

  • Praxis fuer Innere Medizin Haematologie und Internistische Onkologie

    Alsfeld, 36304

  • Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg

    Augsburg, 86150

  • Kreiskrankenhaus Aurich

    Aurich, 26603

  • Klinikum am Bamberg

    Bamberg, 96049

  • Internistische Gemeinschaftspraxis - Berlin

    Berlin, 13347

  • St. Hedwig Krankenhaus

    Berlin, D-10115

  • Internistische Gemeinschaftspraxis Betzdorf

    Betzdorf, D-57518

  • DIAKO Ev. Diakonie Krankenhaus gGmbH

    Bremen, D-28239

  • Onkologische Schwerpunktpraxis at Facharzt fuer Innere Medizin

    Coesfeld, 48653

  • Praxis Fuer Haematologie Internistische Onkologie

    Cologne, D-50677

  • Medizinische Universitaetsklinik I at the University of Cologne

    Cologne, D-50924

  • Universitaetsklinikum Duesseldorf

    Düsseldorf, D-40225

  • Helios Klinikum Erfurt

    Erfurt, 99012

  • Onkologische Schwerpunkt Praxis

    Erlangen, D-91052

  • St. Antonius Hospital

    Eschweiler, DOH-52249

  • Universitaetsklinikum Essen

    Essen, D-45122

  • Internistische Gemeinschaftspraxis - Forchheim

    Forchheim, 91301

  • Klinikum Frankfurt (Oder) GmbH

    Frankfurt (Oder), D-15236

  • Internistische Gemeinschaftspraxis - Friedberg

    Friedberg, 86316

  • Study site

    Fürstenzell, 94981

  • Klinikum Garmisch - Partenkirchen GmbH

    Garmisch-Partenkirchen, D-82467

  • Internistische Praxisgemeinschaft

    Germering, 82110

  • Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie

    Giessen, 35392

  • Universitaetsklinikum Goettingen

    Göttingen, D-37075

  • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet

    Greifswald, D-17475

  • Maria-Josef-Hospital Greven GmbH

    Greven, 48268

  • St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

    Hagen, D-58095

  • Internistische Gemeinschaftspraxis - Halle

    Halle, 06110

  • Universitaetsklinikum Halle

    Halle, D-06120

  • Krankenhaus Siloah - Medizinische Klinik II

    Hanover, D-30449

  • Praxis Dr. med Freddy Henne

    Hechingen, D-72379

  • Universitatsklinikum Heidelberg

    Heidelberg, D-69120

  • Westpfalz-Klinikum GmbH

    Kaiserslautern, D-67653

  • Internistische Gemeinschaftspraxis - Kassel

    Kassel, D-34117

  • University Hospital Schleswig-Holstein - Kiel Campus

    Kiel, D-24116

  • Internistische Onkologische Praxis - Kronach

    Kronach, 96317

  • Internistische Praxis - Landshut

    Landshut, 84028

  • Caritas - Krakenhaus Lebach

    Lebach, 66822

  • Onkologische Schwerpunktpraxis - Leer

    Leer, D-26789

  • Staedtisches Klinikum Magdeburg - Altstadt

    Magdeburg, D-39104

  • Gemeinschaftspraxis

    Mannheim, D-68161

  • Klinikum Minden

    Minden, D-32423

  • Haematologische Praxis - Moenchengladbach

    Mönchengladbach, D-41239

  • Study site

    Monchenglasbach/Rheydt, D-41239

  • Munich Oncologic Practice at Elisenhof

    Munich, D-80335

  • Klinikum Rechts Der Isar - Technische Universitaet Muenchen

    Munich, D-81241

  • Hamatologie/Onkologie Praxisgemeinschaft - Muenchen

    Munich, D-81245

  • Haematologische Schwerpunktpraxis

    Munich, D-81679

  • Klinikum Schwaebisch Gmuend Stauferklinik

    Mutlangen, D-73557

  • Internistische Gemeinschaftspraxis - Offenbach

    Offenbach, D-63065

  • Internistische Gemeinschaftspraxis - Oldenburg

    Oldenburg, D-26121

  • Study site

    Pforzheim, 75179

  • Internistische Schwerpunktpraxis

    Rüsselsheim am Main, 65428

  • Schwerpunktpraxis fuer Haematologie und Onkologie

    Saarbrücken, 66113

  • Diakonie - Krankenhaus

    Schwäbisch Hall, 74523

  • St. Marien - Krankenhaus Siegen GMBH

    Siegen, D-57072

  • Study site

    Singen, D-78224

  • Robert-Bosch-Krankenhaus

    Stuttgart, 70376

  • Diakonie Klinikum Stuttgart

    Stuttgart, D-70176

  • Onkologische Gemeinschaftspraxis - Trier

    Trier, 54290

  • Universitaetsklinikum Tuebingen

    Tübingen, D-72076

  • Praxis fuer Haematologie und Onkologie

    Twistringen, D-27239

  • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

    Ulm, D-89081

  • St. Marienhospital - Vechta

    Vechta, D-49377

  • Burkhard and Reimann Gemeinschaftspraxis

    Worms, DOH-67547

Other trials in Germany

France25 sites

  • Centre Hospitalier Universitaire d'Amiens

    Amiens, 80054

  • Centre Hospitalier Regional et Universitaire d'Angers

    Angers, 49033

  • Centre Hospitalier Victor Dupouy

    Argenteuil, 95107

  • Hopital Avicenne

    Bobigny, 93009

  • CHU de Caen

    Caen, 14033

  • CHR Clermont Ferrand, Hotel Dieu

    Clermont-Ferrand, 63058

  • Centre Hospitalier Universitaire Henri Mondor

    Créteil, 94000

  • CHU de Grenoble - Hopital de la Tronche

    Grenoble, 38043

  • Centre Jean Bernard

    Le Mans, 72000

  • Centre Hospital Universitaire Hop Huriez

    Lille, 59037

  • Hopital Edouard Herriot - Lyon

    Lyon, 69437

  • Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

    Marseille, 13273

  • Centre Hospitalier de Meaux

    Meaux, 77104

  • CHR Hotel Dieu

    Nantes, 44093

  • Hopital Saint-Louis

    Paris, 75475

  • CHU Pitie-Salpetriere

    Paris, 75651

  • Hopital Necker

    Paris, 75743

  • Hopital Haut Leveque

    Pessac, 33604

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69495

  • CHU Poitiers

    Poitiers, 86021

  • CHU - Robert Debre

    Reims, 51092

  • Centre Henri Becquerel

    Rouen, 76038

  • Hopital Universitaire Hautepierre

    Strasbourg, 67098

  • CHU de Toulouse, Hotel Dieu

    Toulouse, 31059

  • CHU de Nancy - Hopitaux de Brabois

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Austria1 site

  • Universitaetsklinik fuer Innere Medizin I

    Vienna, A-1090

Other trials in Austria

About this study

Official title: Randomized Phase III Trial Comparing Early Treatment With Fludarabine/Cyclophosphamide + Rituximab Versus Deferred Treatment in Untreated Binet Stage A Patients With CLL and High Risk of Progression

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether giving rituximab together with fludarabine and cyclophosphamide is more effective than observation alone in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying rituximab, fludarabine, and cyclophosphamide to see how well they work compared to observation alone in treating patients with stage 0, stage I, or stage II B-cell chronic lymphocytic leukemia.

Read the detailed description

OBJECTIVES:

Primary

  • Compare the effect, in terms of event-free survival, of deferred versus immediate treatment with rituximab, fludarabine, and cyclophosphamide in patients with previously untreated Binet stage A chronic lymphocytic leukemia at high risk for disease progression.
  • Investigate and define a new prognostic staging system for patients with Binet stage A chronic lymphocytic leukemia.

Secondary

  • Compare the time to progression to Binet stages B and C in patients treated with these regimens.
  • Compare the overall and progression-free survival of patients treated with these regimens.
  • Compare the quality of life of patients treated with these regimens.
  • Compare the time to treatment in patients treated with these regimens.
  • Analyze the pharmacoeconomics of these regimens in these patients.
  • Determine the overall response rate (partial and complete) in patients included in the early treatment arm.
  • For patients included in the early treatment arm in complete remission, determine the percentage achieving complete molecular remission using the clone-specific CDR-III region as follow-up parameter.
  • Determine the duration of response in patients included in the early treatment arm.
  • Determine any adverse events related to treatment/safety of treatment.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk factor profile (< 2 risk factors [low risk] vs ≥ 2 risk factors [high risk]). Low-risk patients are assigned to arm II. High-risk patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive rituximab IV on day 1, fludarabine IV on days 1-3, and cyclophosphamide IV on days 1-3. Treatment repeats every 28 days for up to 6 courses.
  • Arm II: Patients undergo observation only until disease progression.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.

Keywords
stage 0 chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

    Also called Fludura

    cycles 1-6: 25 mg/m² i.v., d2-4, q28d

  • CyclophosphamideDrug

    Also called Endoxan

    cycles 1-6: 250 mg/m² i.v., d2-4, q28d

  • RituximabBiological

    Also called Mabthera, Rituxan

    cycle1: 375 mg/m² i.v., d1, q28d

    cycles 2-6: 500 mg/m² i.v., d1, q28d

Study groups in NCT00275054
Study groupRoleWhat they receive
Cohort I (FCR)ExperimentalPatients with 2 or more risk factors out of 4 (1. unfavorable molecular cytogenetics, 2. high serum thymidine kinase levels, 3. lymphocyte doubling time shorter than 12 months, 4. unmutated IgVH gene) who are randomized into cohort I receive Fludarabine, Cyclophosphamide and Rituximab (FCR) chemoimmunotherapy.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Rituximab
Cohort II (W&W)No interventionPatients with 2 or more risk factors out of 4 (1. unfavorable molecular cytogenetics, 2. high serum thymidine kinase levels, 3. lymphocyte doubling time shorter than 12 months, 4. unmutated IgVH gene) who are randomized into cohort II receive no treatment at all (watch \& wait).
Cohort III (W&W)No interventionPatients with less than 2 risk factors out of 4 (1. unfavorable molecular cytogenetics, 2. high serum thymidine kinase levels, 3. lymphocyte doubling time shorter than 12 months, 4. unmutated IgVH gene) are assigned directly to cohort III and receive no treatment at all (watch \& wait).

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival

  2. Development of a new prognostic staging system

Secondary outcomes (10)

  1. Progression free survival

  2. Overall survival

  3. Time to progression to Binet stages B and C

  4. Time to treatment

  5. Quality of life

  6. Pharmacoeconomic analysis

  7. Overall response (complete and partial) rate in patients in the early treatment arm

  8. Percentage of patients achieving complete molecular remission in the early treatment arm

  9. Duration of response in patients in the early treatment arm

  10. Adverse events in patients in the early treatment arm

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jan 2006 (estimated)
  2. Study startOct 2005
  3. Primary completionJul 2007
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
825 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00275054
Sponsor's protocol ID
CLL7
Other IDs
EU-20559, ROCHE-GCLLSG-CLL7, 2005-003018-14, 2005
Status last verified
May 2019
First submitted
10 Jan 2006
Last updated
23 May 2019
Results posted
No
Individual data sharing
No

Publications

  • Sachanas S, Pangalis GA, Fink AM, Bahlo J, Fischer K, Levidou G, Kyrtsonis MC, Bartzi V, Vassilakopoulos TP, Kalpadakis C, Koulieris E, Moschogiannis M, Yiakoumis X, Tsirkinidis P, Angelopoulou MK, Eichhorst B, Hallek M. Small Lymphocytic Lymphoma: Analysis of Two Cohorts Including Patients in Clinical Trials of the German Chronic Lymphocytic Leukemia Study Group (GCLLSG) or in "Real-Life" Outside of Clinical Trials. Anticancer Res. 2019 May;39(5):2591-2598. doi: 10.21873/anticanres.13382.

    PubMed 31092457

  • Herling CD, Cymbalista F, Gross-Ophoff-Muller C, Bahlo J, Robrecht S, Langerbeins P, Fink AM, Al-Sawaf O, Busch R, Porcher R, Cazin B, Dreyfus B, Ibach S, Lepretre S, Fischer K, Kaiser F, Eichhorst B, Wentner CM, Hoechstetter MA, Dohner H, Leblond V, Kneba M, Letestu R, Bottcher S, Stilgenbauer S, Hallek M, Levy V. Early treatment with FCR versus watch and wait in patients with stage Binet A high-risk chronic lymphocytic leukemia (CLL): a randomized phase 3 trial. Leukemia. 2020 Aug;34(8):2038-2050. doi: 10.1038/s41375-020-0747-7. Epub 2020 Feb 18.

    PubMed 32071431

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fludarabine, Cyclophosphamide and Rituximab in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 91 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 91 sites in Germany, France, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00275054, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in