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

This study has been completed.
Sponsor:
Collaborator:
University of Cologne
Information provided by (Responsible Party):
German CLL Study Group
ClinicalTrials.gov Identifier:
NCT00274989
First received: January 10, 2006
Last updated: September 30, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Bendamustine
Biological: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by German CLL Study Group:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: 56 days after the last of six cycles ] [ Designated as safety issue: No ]
    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).


Enrollment: 195
Study Start Date: November 2005
Study Completion Date: March 2011
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: MabThera, Rituxan

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274989

  Show 58 Study Locations
Sponsors and Collaborators
German CLL Study Group
University of Cologne
Investigators
Study Chair: Clemens M. Wendtner Medizinische Universitaetsklinik I at the University of Cologne
  More Information

Additional Information:
Publications:
Responsible Party: German CLL Study Group
ClinicalTrials.gov Identifier: NCT00274989     History of Changes
Other Study ID Numbers: CLL2M  EU-20552  ROCHE-GCLLSG-CLL2M  2005-001596-34 
Study First Received: January 10, 2006
Last Updated: September 30, 2016
Health Authority: Germany: Paul-Ehrlich-Institut
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by German CLL Study Group:
B-cell chronic lymphocytic leukemia
relapsed refractory chronic lymphocytic leukemia
previously untreated chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016