Bendamustine and Rituximab in Treating Patients With Previously Untreated or Relapsed Chronic Lymphocytic Leukemia

NCT ID: NCT00274989

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 195 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2011-03-31

Brief Summary

CLL2M is a phase 2, multicenter, open label study to investigate the possible therapeutic benefits of using bendamustine in combination with rituximab for the treatment of patients with previously untreated or relapsed CLL.

Detailed Description

Conventional chemotherapy and also high dose chemotherapy with autologous stem cell transplantation are not curative treatment options in B-CLL; nearly all patients will eventually relapse. Also monoclonal antibodies are not curative for B-CLL patients in monotherapy, their impact on survival in combination with conventional chemotherapy is currently validated. In addition, there is no standard combination therapy for patients with relapsed CLL. Therefore there is an urgent medical need to identify new strategies.

The combination of rituximab (monoclonal antibody) and bendamustine (chemotherapy) has shown encouraging activity in patients with relapsed/refractory NHL or mantle cell lymphoma. In vitro studies have been used to investigate the effects of bendamustine and rituximab on programmed cell death (apoptosis) and have shown synergistic effects of both drugs. The mechanisms of action of these two active drugs may provide a treatment with good therapeutic potential in CLL. However, though bendamustine has been used for over 30 years there is still a need to define a standard regimen for the use of bendamustine in combination with monoclonal antibodies (mAb) especially in the treatment of CLL.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bendamustine plus Rituximab

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: DRUG

First-Line Therapy: Bendamustine i.v. 90 mg/m² day 1-2, q4wks, cycle 1 to 6

2nd to 4th -Line Therapy: Bendamustine i.v. 70 mg/m² day 1-2 q4wks, cycle 1 to 6

Rituximab

Intervention Type: BIOLOGICAL

First-Line Therapy: Rituximab i.v. 375 mg/m² day 0, q4wks, cycle 1; Rituximab i.v. 500 mg/m² day 1, q4wks, cycle 2-6

2nd to 4th -Line Therapy: Rituximab i.v. 375 mg/m² day 0, q4wks, cycle 1; Rituximab i.v. 500 mg/m² day 1, q4wks, cycle 2-6

Interventions

Bendamustine

First-Line Therapy: Bendamustine i.v. 90 mg/m² day 1-2, q4wks, cycle 1 to 6

2nd to 4th -Line Therapy: Bendamustine i.v. 70 mg/m² day 1-2 q4wks, cycle 1 to 6

Intervention Type: DRUG

Rituximab

First-Line Therapy: Rituximab i.v. 375 mg/m² day 0, q4wks, cycle 1; Rituximab i.v. 500 mg/m² day 1, q4wks, cycle 2-6

2nd to 4th -Line Therapy: Rituximab i.v. 375 mg/m² day 0, q4wks, cycle 1; Rituximab i.v. 500 mg/m² day 1, q4wks, cycle 2-6

Intervention Type: BIOLOGICAL

Other Intervention Names

MabThera, Rituxan

Eligibility Criteria

Inclusion Criteria

• 18 years of age or older
• Diagnosis of B-CLL in need of treatment

• Previously untreated Binet stage C or Binet B with need of treatment according to NCI-criteria
• Relapsed or refractory disease after at least one but not more than 3 prior regimens. Patients who previously received bendamustine must have had at least a partial response with duration of response of at least six months.
• World Health Organization performance status of 0-2
• Life expectancy >12 weeks
• Anti-cancer therapy, major surgery, or irradiation was completed >3 weeks before registration in this study. Patient must have recovered from the acute side effects incurred as a result of previous therapy.
• Serum creatinine ≤1.5 the institutional upper limit of normal (ULN) or Creatinine clearance >30 ml/min/1.73 m²
• Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 the institutional ULN value, unless directly attributable to the patient's tumor.
• Female patients with childbearing potential must have a negative serum pregnancy test within two weeks of first dose of study drug(s). Male and female patients must agree to use an effective contraceptive method while on study treatment and for a minimum of six months following study therapy.
• Signed, written informed consent.

Exclusion Criteria

• Previously treated with >3 prior regimens for B-CLL.
• Known central nervous system (CNS) involvement with B-CLL.
• Patients who have progressed with more aggressive B-cell cancers such as Richter's syndrome.
• History of anaphylaxis following exposure to monoclonal antibodies.
• Known to be human immunodeficiency virus (HIV), hepatitis B, or C positive.
• Active infection or history of severe infection (grade 4) within 3 months prior to study registration.
• Medical condition requiring prolonged use of oral corticosteroids (> 1 month).
• Use of investigational agents within 30 days prior to study randomization.
• Active secondary malignancy.
• ANC <1.5x109/L or platelet count <75x109/L, unless due to bone marrow involvement of CLL.
• Other severe, concurrent diseases, including tuberculosis, mental disorders, serious cardiac functional capacity (Class III or IV as defined by the New York Heart Association Classification), severe diabetes, severe hypertension, pulmonary disease (chronic obstructive pulmonary disease [COPD] with hypoxemia), or major organ malfunction (liver, kidney) that could interfere with the patient's ability to participate in the study.
• Pregnant or nursing women.
• Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.
• Participation in another clinical trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cologne

OTHER

Sponsor Role: collaborator

German CLL Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clemens M. Wendtner

Role: STUDY_CHAIR

Medizinische Universitaetsklinik I at the University of Cologne

Locations

Internistische Praxis - Arnstadt

Arnstadt, , Germany

Klinikum Augsburg

Augsburg, , Germany

HELIOS Klinikum Bad Saarow

Bad Saarow, , Germany

Internistische Gemeinschaftspraxis - Berlin

Berlin, , Germany

Charite - Campus Charite Mitte

Berlin, , Germany

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, , Germany

Charite University Hospital - Campus Virchow Klinikum

Berlin, , Germany

Augusta-Kranken-Anstalt gGmbH

Bochum, , Germany

Marienhospital Bottrop gGmbH

Bottrop, , Germany

DIAKO Ev. Diakonie Krankenhaus gGmbH

Bremen, , Germany

Medizinische Universitaetsklinik I at the University of Cologne

Cologne, , Germany

Klinikum Darmstadt

Darmstadt, , Germany

Krankenhaus Benrath

Düsseldorf, , Germany

Helios Klinikum Erfurt

Erfurt, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Staedtische Kliniken Esslingen

Esslingen am Neckar, , Germany

Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), , Germany

Klinikum Garmisch - Partenkirchen GmbH

Garmisch-Partenkirchen, , Germany

Internistische Praxisgemeinschaft

Germering, , Germany

Universitaetsklinikum Goettingen

Göttingen, , Germany

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

Greifswald, , Germany

Allgemeines Krankenhaus Hagen

Hagen, , Germany

Praxis fur Innere Medizin - Hamburg

Hamburg, , Germany

Hamatologische/Onkologische - Hamburg

Hamburg, , Germany

Asklepios Klinik St. Georg

Hamburg, , Germany

Evangelische Krankenhaus Hamm

Hamm, , Germany

Universitaetsklinikum des Saarlandes

Homburg, , Germany

Westpfalz-Klinikum GmbH

Kaiserslautern, , Germany

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, , Germany

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, , Germany

Onkologische Schwerpunktpraxis - Leer

Leer, , Germany

Klinikum Lippe - Lemgo

Lemgo, , Germany

Gemeinschaftspraxis - Ludwigshafen

Ludwigshafen, , Germany

Kreiskrankenhaus Luedenscheid

Lüdenscheid, , Germany

Staedtisches Klinikum Magdeburg

Magdeburg, , Germany

Krankenhaus Maria Hilf GmbH

Mönchengladbach, , Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Haematologisch - Onkologische Gemeinschaftspraxis - Muenster

Münster, , Germany

Onkologische Schwerpunktpraxis Dr. Schmidt

Neunkirchen, , Germany

Klinikum Oldenburg

Oldenburg, , Germany

Paracelsus Karankenhaus Ruit

Ostfildern, , Germany

Gemeinschaftspraxis - Pinneberg

Pinnebeg, , Germany

Klinikum Ernst Von Bergmann

Potsdam, , Germany

Scherpunktpraxis fur Hematologie und Onkologie

Regensburg, , Germany

Klinikum der Universitaet Regensburg

Regensburg, , Germany

Krankenhaus Barmherzige Brueder Regensburg

Regensburg, , Germany

Internistische Praxis Dres. Hempel und Hochdorfer

Rehling, , Germany

Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock

Rostock, , Germany

Caritasklinik St. Theresia

Saarbrücken, , Germany

Schwerpunktpraxis fur Hamatologie und Onkologie

Siegburg, , Germany

St. Marien - Krankenhaus Siegen GMBH

Siegen, , Germany

Hanse-Klinikum Stralsund - Krankenhaus West

Stralsund, , Germany

Haematologische Praxis

Stuttgart, , Germany

Krankenanstalt Mutterhaus der Borromaerinnen

Trier, , Germany

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Ulm, , Germany

St. Marienhospital - Vechta

Vechta, , Germany

Heinrich-Braun-Krankenhaus Zwickau

Zwickau, , Germany

Countries

Germany

References

Al-Sawaf O, Robrecht S, Bahlo J, Fink AM, Cramer P, von Tresckow J, Maurer C, Bergmann M, Seiler T, Lange E, Kneba M, Stilgenbauer S, Dohner H, Kiehl MG, Jager U, Wendtner CM, Fischer K, Goede V, Hallek M, Eichhorst B, Hopfinger G. Impact of gender on outcome after chemoimmunotherapy in patients with chronic lymphocytic leukemia: a meta-analysis by the German CLL study group. Leukemia. 2017 Oct;31(10):2251-2253. doi: 10.1038/leu.2017.221. Epub 2017 Jul 12. No abstract available.

Reference Type: BACKGROUND

PMID: 28745332 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31092457 (View on PubMed)

Fischer K, Cramer P, Busch R, Stilgenbauer S, Bahlo J, Schweighofer CD, Bottcher S, Staib P, Kiehl M, Eckart MJ, Kranz G, Goede V, Elter T, Buhler A, Winkler D, Kneba M, Dohner H, Eichhorst BF, Hallek M, Wendtner CM. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2011 Sep 10;29(26):3559-66. doi: 10.1200/JCO.2010.33.8061. Epub 2011 Aug 15.

Reference Type: RESULT

PMID: 21844497 (View on PubMed)

Fischer K, Cramer P, Busch R, Bottcher S, Bahlo J, Schubert J, Pfluger KH, Schott S, Goede V, Isfort S, von Tresckow J, Fink AM, Buhler A, Winkler D, Kreuzer KA, Staib P, Ritgen M, Kneba M, Dohner H, Eichhorst BF, Hallek M, Stilgenbauer S, Wendtner CM. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2012 Sep 10;30(26):3209-16. doi: 10.1200/JCO.2011.39.2688. Epub 2012 Aug 6.

Reference Type: RESULT

PMID: 22869884 (View on PubMed)

Other Identifiers

EU-20552

Identifier Type: -

Identifier Source: secondary_id

ROCHE-GCLLSG-CLL2M

Identifier Type: -

Identifier Source: secondary_id

2005-001596-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLL2M

Identifier Type: -

Identifier Source: org_study_id