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

May 21, 2019 updated by: German CLL Study Group

Multicentre Phase II Trial of Bendamustine in Combination With Rituximab for Patients With Previously Untreated or Relapsed Chronic Lymphocytic Leukemia. CLL2M Protocol of the German CLL-Study Group (GCLLSG)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

195

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Arnstadt, Germany, 99310
        • Internistische Praxis - Arnstadt
      • Augsburg, Germany, D-86156
        • Klinikum Augsburg
      • Bad Saarow, Germany, 15526
        • Helios Klinikum Bad Saarow
      • Berlin, Germany, D-13353
        • Charite University Hospital - Campus Virchow Klinikum
      • Berlin, Germany, D-10117
        • Charité - Campus Charité Mitte
      • Berlin, Germany, D-12200
        • Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
      • Berlin, Germany, 13347
        • Internistische Gemeinschaftspraxis - Berlin
      • Bochum, Germany, D-44791
        • Augusta-Kranken-Anstalt gGmbH
      • Bottrop, Germany, D-46236
        • Marienhospital Bottrop gGmbH
      • Bremen, Germany, D-28239
        • DIAKO Ev. Diakonie Krankenhaus gGmbH
      • Cologne, Germany, D-50924
        • Medizinische Universitaetsklinik I at the University of Cologne
      • Darmstadt, Germany, D-64283
        • Klinikum Darmstadt
      • Dusseldorf, Germany, 40593
        • Krankenhaus Benrath
      • Erfurt, Germany, 99012
        • Helios Klinikum Erfurt
      • Essen, Germany, D-45122
        • Universitaetsklinikum Essen
      • Esslingen, Germany, D-73730
        • Staedtische Kliniken Esslingen
      • Frankfurt (Oder), Germany, D-15236
        • Klinikum Frankfurt (Oder) GmbH
      • Garmisch-Partenkirchen, Germany, D-82467
        • Klinikum Garmisch - Partenkirchen GmbH
      • Germering, Germany, 82110
        • Internistische Praxisgemeinschaft
      • Goettingen, Germany, D-37075
        • Universitaetsklinikum Goettingen
      • Greifswald, Germany, D-17475
        • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
      • Hagen, Germany, D-58095
        • Allgemeines Krankenhaus Hagen
      • Hamburg, Germany, D-20099
        • Asklepios Klinik St. Georg
      • Hamburg, Germany, 22457
        • Praxis fur Innere Medizin - Hamburg
      • Hamburg, Germany, 22767
        • Hamatologische/Onkologische - Hamburg
      • Hamm, Germany, DOH-59063
        • Evangelische Krankenhaus Hamm
      • Homburg, Germany, D-66424
        • Universitaetsklinikum des Saarlandes
      • Kaiserslautern, Germany, D-67653
        • Westpfalz-Klinikum GmbH
      • Karlsruhe, Germany, 76133
        • Staedtisches Klinikum Karlsruhe gGmbH
      • Kiel, Germany, D-24116
        • University Hospital Schleswig-Holstein - Kiel Campus
      • Leer, Germany, D-26789
        • Onkologische Schwerpunktpraxis - Leer
      • Lemgo, Germany, D-32657
        • Klinikum Lippe - Lemgo
      • Ludwigshafen, Germany, 67061
        • Gemeinschaftspraxis - Ludwigshafen
      • Luedenscheid, Germany, 58515
        • Kreiskrankenhaus Luedenscheid
      • Magdeburg, Germany, D-39130
        • Staedtisches Klinikum Magdeburg
      • Moenchengladbach, Germany, D-41063
        • Krankenhaus Maria Hilf GmbH
      • Muenster, Germany, D-48149
        • Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
      • Munich, Germany, D-81377
        • Klinikum der Universitaet Muenchen - Grosshadern Campus
      • Neunkirchen, Germany, D-66538
        • Onkologische Schwerpunktpraxis Dr. Schmidt
      • Oldenburg, Germany, D-26133
        • Klinikum Oldenburg
      • Ostfildern, Germany, 73760
        • Paracelsus Karankenhaus Ruit
      • Pinnebeg, Germany, 25421
        • Gemeinschaftspraxis - Pinneberg
      • Potsdam, Germany, D-14467
        • Klinikum Ernst von Bergmann
      • Regensburg, Germany, D-93049
        • Krankenhaus Barmherzige Brueder Regensburg
      • Regensburg, Germany, D-93042
        • Klinikum der Universitaet Regensburg
      • Regensburg, Germany, 93053
        • Scherpunktpraxis fur Hematologie und Onkologie
      • Rehling, Germany, 86508
        • Internistische Praxis Dres. Hempel und Hochdorfer
      • Rostock, Germany, D-18057
        • Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
      • Saarbrucken, Germany, D-66113
        • Caritasklinik St. Theresia
      • Siegburg, Germany, 53721
        • Schwerpunktpraxis für Hämatologie und Onkologie
      • Siegen, Germany, D-57072
        • St. Marien - Krankenhaus Siegen GMBH
      • Stralsund, Germany, D-18437
        • Hanse-Klinikum Stralsund - Krankenhaus West
      • Stuttgart, Germany, D-70173
        • Haematologische Praxis
      • Trier, Germany, D-54290
        • Krankenanstalt Mutterhaus der Borromaerinnen
      • Tuebingen, Germany, D-72076
        • Universitaetsklinikum Tuebingen
      • Ulm, Germany, D-89081
        • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
      • Vechta, Germany, D-49377
        • St. Marienhospital - Vechta
      • Zwickau, Germany, 08060
        • Heinrich-Braun-Krankenhaus Zwickau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bendamustine plus Rituximab
Drug: 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

Biological: 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

Other Names:
  • MabThera, Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate
Time Frame: 56 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).
56 days after the last of six cycles

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German CLL Study Group

Collaborators

University of Cologne

Investigators

  • Study Chair: Clemens M. Wendtner, Medizinische Universitaetsklinik I at the University of Cologne

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

January 10, 2006

First Submitted That Met QC Criteria

January 10, 2006

First Posted (Estimate)

January 11, 2006

Study Record Updates

Last Update Posted (Actual)

May 23, 2019

Last Update Submitted That Met QC Criteria

May 21, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLL2M
  • EU-20552
  • ROCHE-GCLLSG-CLL2M
  • 2005-001596-34 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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