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

Chronic Lymphocytic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00274989
• Other study ID #: CLL2M
• Secondary ID: EU-20552ROCHE-GC
• Status: Completed
• Phase: Phase 2
• Start date: November 2005
• Est. completion date: March 2011

Study information

• Verified date: May 2019
• Source: German CLL Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: March 2011
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

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

Locations

Country	Name	City	State
Germany	Internistische Praxis - Arnstadt	Arnstadt
Germany	Klinikum Augsburg	Augsburg
Germany	HELIOS Klinikum Bad Saarow	Bad Saarow
Germany	Charite - Campus Charite Mitte	Berlin
Germany	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Charite University Hospital - Campus Virchow Klinikum	Berlin
Germany	Internistische Gemeinschaftspraxis - Berlin	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	Dusseldorf
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Universitaetsklinikum Essen	Essen
Germany	Staedtische Kliniken Esslingen	Esslingen
Germany	Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)
Germany	Klinikum Garmisch - Partenkirchen GmbH	Garmisch-Partenkirchen
Germany	Internistische Praxisgemeinschaft	Germering
Germany	Universitaetsklinikum Goettingen	Goettingen
Germany	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Allgemeines Krankenhaus Hagen	Hagen
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Hamatologische/Onkologische - Hamburg	Hamburg
Germany	Praxis fur Innere Medizin - Hamburg	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	Luedenscheid
Germany	Staedtisches Klinikum Magdeburg	Magdeburg
Germany	Krankenhaus Maria Hilf GmbH	Moenchengladbach
Germany	Haematologisch - Onkologische Gemeinschaftspraxis - Muenster	Muenster
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
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	Klinikum der Universitaet Regensburg	Regensburg
Germany	Krankenhaus Barmherzige Brueder Regensburg	Regensburg
Germany	Scherpunktpraxis fur Hematologie und Onkologie	Regensburg
Germany	Internistische Praxis Dres. Hempel und Hochdorfer	Rehling
Germany	Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock	Rostock
Germany	Caritasklinik St. Theresia	Saarbrucken
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	Tuebingen
Germany	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Ulm
Germany	St. Marienhospital - Vechta	Vechta
Germany	Heinrich-Braun-Krankenhaus Zwickau	Zwickau

Sponsors (2)

Lead Sponsor	Collaborator
German CLL Study Group	University of Cologne

Country where clinical trial is conducted

Germany, 

References & Publications (4)

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, Döhner H, Kiehl MG, Jäger 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. — View Citation

Fischer K, Cramer P, Busch R, Böttcher S, Bahlo J, Schubert J, Pflüger KH, Schott S, Goede V, Isfort S, von Tresckow J, Fink AM, Bühler A, Winkler D, Kreuzer KA, Staib P, Ritgen M, Kneba M, Döhner H, Eichhorst BF, Hallek M, Stilgenbauer S, Wendtner CM. Be — View Citation

Fischer K, Cramer P, Busch R, Stilgenbauer S, Bahlo J, Schweighofer CD, Böttcher S, Staib P, Kiehl M, Eckart MJ, Kranz G, Goede V, Elter T, Bühler A, Winkler D, Kneba M, Döhner H, Eichhorst BF, Hallek M, Wendtner CM. Bendamustine combined with rituximab i — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	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

External Links

•   Click here for more information about this study: CLL2M (German CLL Study Group)