Clinical trial NCT00274989: Bendamustine and Rituximab in Treating Patients With Previously Untreated or Relapsed Chronic Lymphocytic Leukemia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: B-cell chronic lymphocytic leukemia
relapsed refractory chronic lymphocytic leukemia
previously untreated chronic lymphocytic leukemia
Lead sponsor: German CLL Study Group
Sponsor class: OTHER
Collaborators: name: University of Cologne
First posted: 2006-01-11
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall response rate
timeFrame: 56 days after the last of six cycles
Secondary outcomes:
Other outcomes:
Locations:
city: Arnstadt
country: Germany
facility: Internistische Praxis - Arnstadt
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Bad Saarow
country: Germany
facility: HELIOS Klinikum Bad Saarow
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charite University Hospital - Campus Virchow Klinikum
city: Bochum
country: Germany
facility: Augusta-Kranken-Anstalt gGmbH
city: Bottrop
country: Germany
facility: Marienhospital Bottrop gGmbH
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie Krankenhaus gGmbH
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Dusseldorf
country: Germany
facility: Krankenhaus Benrath
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Esslingen
country: Germany
facility: Staedtische Kliniken Esslingen
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Garmisch-Partenkirchen
country: Germany
facility: Klinikum Garmisch - Partenkirchen GmbH
city: Germering
country: Germany
facility: Internistische Praxisgemeinschaft
city: Goettingen
country: Germany
facility: Universitaetsklinikum Goettingen
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Hagen
country: Germany
facility: Allgemeines Krankenhaus Hagen
city: Hamburg
country: Germany
facility: Praxis fur Innere Medizin - Hamburg
city: Hamburg
country: Germany
facility: Hamatologische/Onkologische - Hamburg
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Hamm
country: Germany
facility: Evangelische Krankenhaus Hamm
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe gGmbH
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein - Kiel Campus
city: Leer
country: Germany
facility: Onkologische Schwerpunktpraxis - Leer
city: Lemgo
country: Germany
facility: Klinikum Lippe - Lemgo
city: Ludwigshafen
country: Germany
facility: Gemeinschaftspraxis - Ludwigshafen
city: Luedenscheid
country: Germany
facility: Kreiskrankenhaus Luedenscheid
city: Magdeburg
country: Germany
facility: Staedtisches Klinikum Magdeburg
city: Moenchengladbach
country: Germany
facility: Krankenhaus Maria Hilf GmbH
city: Muenster
country: Germany
facility: Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Neunkirchen
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. Schmidt
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Ostfildern
country: Germany
facility: Paracelsus Karankenhaus Ruit
city: Pinnebeg
country: Germany
facility: Gemeinschaftspraxis - Pinneberg
city: Potsdam
country: Germany
facility: Klinikum Ernst Von Bergmann
city: Regensburg
country: Germany
facility: Scherpunktpraxis fur Hematologie und Onkologie
city: Regensburg
country: Germany
facility: Klinikum der Universitaet Regensburg
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brueder Regensburg
city: Rehling
country: Germany
facility: Internistische Praxis Dres. Hempel und Hochdorfer
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
city: Saarbrucken
country: Germany
facility: Caritasklinik St. Theresia
city: Siegburg
country: Germany
facility: Schwerpunktpraxis fur Hamatologie und Onkologie
city: Siegen
country: Germany
facility: St. Marien - Krankenhaus Siegen GMBH
city: Stralsund
country: Germany
facility: Hanse-Klinikum Stralsund - Krankenhaus West
city: Stuttgart
country: Germany
facility: Haematologische Praxis
city: Trier
country: Germany
facility: Krankenanstalt Mutterhaus der Borromaerinnen
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Ulm
country: Germany
facility: Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
city: Vechta
country: Germany
facility: St. Marienhospital - Vechta
city: Zwickau
country: Germany
facility: Heinrich-Braun-Krankenhaus Zwickau
Study officials:
affiliation: Medizinische Universitaetsklinik I at the University of Cologne
name: Clemens M. Wendtner
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.