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

Phase 2
Completed
Conditions
Chronic Lymphocytic Leukemia
Interventions
Biological: Rituximab
Registration Number
NCT00274989
Lead Sponsor
German CLL Study Group
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
195
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Bendamustine plus RituximabRituximab-
Bendamustine plus RituximabBendamustine-
Primary Outcome Measures
NameTimeMethod
Overall response rate56 days after the last of six cycles

Response will be assessed using clinical examination, hematology, bone marrow examination, plain radiograph of the chest (chest X-ray), ultrasound or CT of the abdomen, and MRD testing (for the molecular response rate only).

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (58)

HELIOS Klinikum Bad Saarow

🇩🇪

Bad Saarow, Germany

Internistische Praxis - Arnstadt

🇩🇪

Arnstadt, Germany

Klinikum Augsburg

🇩🇪

Augsburg, Germany

University Hospital Schleswig-Holstein - Kiel Campus

🇩🇪

Kiel, Germany

Staedtisches Klinikum Karlsruhe gGmbH

🇩🇪

Karlsruhe, Germany

Onkologische Schwerpunktpraxis - Leer

🇩🇪

Leer, Germany

Praxis fur Innere Medizin - Hamburg

🇩🇪

Hamburg, Germany

Universitaetsklinikum des Saarlandes

🇩🇪

Homburg, Germany

Evangelische Krankenhaus Hamm

🇩🇪

Hamm, Germany

Gemeinschaftspraxis - Ludwigshafen

🇩🇪

Ludwigshafen, Germany

Klinikum der Universitaet Regensburg

🇩🇪

Regensburg, Germany

Westpfalz-Klinikum GmbH

🇩🇪

Kaiserslautern, Germany

Haematologisch - Onkologische Gemeinschaftspraxis - Muenster

🇩🇪

Muenster, Germany

Klinikum Ernst Von Bergmann

🇩🇪

Potsdam, Germany

Kreiskrankenhaus Luedenscheid

🇩🇪

Luedenscheid, Germany

Klinikum Lippe - Lemgo

🇩🇪

Lemgo, Germany

Onkologische Schwerpunktpraxis Dr. Schmidt

🇩🇪

Neunkirchen, Germany

Gemeinschaftspraxis - Pinneberg

🇩🇪

Pinnebeg, Germany

Paracelsus Karankenhaus Ruit

🇩🇪

Ostfildern, Germany

Staedtisches Klinikum Magdeburg

🇩🇪

Magdeburg, Germany

Universitaetsklinikum Tuebingen

🇩🇪

Tuebingen, Germany

Krankenanstalt Mutterhaus der Borromaerinnen

🇩🇪

Trier, Germany

St. Marienhospital - Vechta

🇩🇪

Vechta, Germany

Schwerpunktpraxis fur Hamatologie und Onkologie

🇩🇪

Siegburg, Germany

Scherpunktpraxis fur Hematologie und Onkologie

🇩🇪

Regensburg, Germany

Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock

🇩🇪

Rostock, Germany

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

🇩🇪

Ulm, Germany

Krankenhaus Maria Hilf GmbH

🇩🇪

Moenchengladbach, Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

🇩🇪

Munich, Germany

Klinikum Oldenburg

🇩🇪

Oldenburg, Germany

St. Marien - Krankenhaus Siegen GMBH

🇩🇪

Siegen, Germany

Heinrich-Braun-Krankenhaus Zwickau

🇩🇪

Zwickau, 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

Medizinische Universitaetsklinik I at the University of Cologne

🇩🇪

Cologne, Germany

Klinikum Darmstadt

🇩🇪

Darmstadt, Germany

Universitaetsklinikum Essen

🇩🇪

Essen, Germany

DIAKO Ev. Diakonie Krankenhaus gGmbH

🇩🇪

Bremen, Germany

Krankenhaus Benrath

🇩🇪

Dusseldorf, Germany

Helios Klinikum Erfurt

🇩🇪

Erfurt, Germany

Staedtische Kliniken Esslingen

🇩🇪

Esslingen, Germany

Universitaetsklinikum Goettingen

🇩🇪

Goettingen, Germany

Klinikum Frankfurt (Oder) GmbH

🇩🇪

Frankfurt (Oder), Germany

Internistische Praxisgemeinschaft

🇩🇪

Germering, Germany

Hamatologische/Onkologische - Hamburg

🇩🇪

Hamburg, Germany

Klinikum Garmisch - Partenkirchen GmbH

🇩🇪

Garmisch-Partenkirchen, Germany

Allgemeines Krankenhaus Hagen

🇩🇪

Hagen, Germany

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

🇩🇪

Greifswald, Germany

Asklepios Klinik St. Georg

🇩🇪

Hamburg, Germany

Krankenhaus Barmherzige Brueder Regensburg

🇩🇪

Regensburg, Germany

Internistische Praxis Dres. Hempel und Hochdorfer

🇩🇪

Rehling, Germany

Caritasklinik St. Theresia

🇩🇪

Saarbrucken, Germany

Hanse-Klinikum Stralsund - Krankenhaus West

🇩🇪

Stralsund, Germany

Haematologische Praxis

🇩🇪

Stuttgart, Germany

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