A Study of MabThera Added to Bendamustine or Chlorambucil in Patients With Chronic Lymphocytic Leukemia (MaBLe).

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 240

Inclusion Criteria

1. Signed and dated written informed consent.
2. 18 years of age or older.
3. Tumor cell phenotype consistent with CLL: CD5+ CD19+, and CD23+.
4. Patients with active CLL (Binet B and C) who require therapy per criteria according to the National Cancer Institute (NCI) criteria 2008.
5. Eastern Cooperative Oncology Group (ECOG) performance status of = 2.
6. Ineligible for treatment with fludarabine. Reasons can be:
a) Concurrent medical conditions, such as history of opportunistic infections, repeated grade 3 or 4 infections of other types,
b) Patients with severe impairment of bone marrow (BM) function (thrombocytopenia, anemia, and/or granulocytopenia), other than for reasons of underlying disease (CLL),
c) Immunodeficiency,
d) Elderly persons (= 75 years) since there are limited data for the use of fludarabine in this population,
e) Previous history of autoimmune processes or positive Coombs test status,
f) Autoimmune phenomena (e.g., autoimmune hemolytic anemia, autoimmune thrombocytopenia, thrombocytopenic purpura, pemphigus, Evans’ syndrome),
g) Judgment of the treating physician.
7. A negative serum pregnancy test within 1 week before the first cycle of treatment must be available for women who are = 2 years after the onset of menopause and not sterilized surgically.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 168

Exclusion Criteria

1. From amendment No. 2, patients already treated for their CLL (second-line patients) will not be allowed to enter in the study.
2. Any other concomitant anti-cancer therapy (e.g., chemotherapy, monoclonal antibodies, signal transduction inhibitors or antineoplastic hormones). Corticosteroids are allowed if they are given for reasons other than CLL and the dose is = 20 mg of prednisolone-equivalent /day.
3. Patients with transformation to aggressive B-cell malignancy (e.g., large B-cell lymphoma, Richter’s syndrome or B-cell prolymphocytic leukemia [PLL]).
4. Known or suspected central nervous system (CNS) involvement of CLL.
5. Any other malignancy within 5 years prior to enrolment except curatively treated carcinoma in situ of the cervix, squamous cell carcinoma of the skin, or basal cell skin cancer. Cervical carcinoma stage 1B or less, breast cancer in situ, or localized prostate cancer stage T1c or less may be considered, provided that the patient was treated with curative intent and was relapse-free for at least 2 years prior to enrolment.
6. Major surgery (excluding lymph node biopsy) within 28 days prior to first cycle of study treatment.
7. Chronic or ongoing active infectious disease requiring systemic treatment, e.g., osteomyelitis.
8. History of clinically significant cerebrovascular disease with residual sequelae: e.g., prolonged reversible ischemic neurologic deficit or stroke (hemorrhagic or ischemic).
9. Patients who have known human immuno-deficiency virus infection or active hepatitis B virus or hepatitis C virus infection.
10. Serious underlying medical conditions, which could impair the ability of the patient to participate in the study (e.g., uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease, uncontrolled hypertension or pre-existing cardiac condition, severe chronic obstructive pulmonary disease with hypoxemia, or major organ malfunction [liver, kidney]). The investigator’s judgment should be exercised.
11. Screening laboratory values: check all laboratory values for adequate renal and hepatic function a) Creatinine clearance (CrCl) <30ml/minutes, b) Total bilirubin > 1.5 times upper limit of normal (ULN), c) Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2.5 times ULN, d) Alkaline phosphatase > 2.5 times ULN.
12. Inadequate hematological function: a) Absolute Neutrophil Count (ANC) < 1.0 × 10exp9/L, unless due to involvement of BM by CLL, b) Platelet count < 50 × 10exp9/L, unless due to involvement of BM by CLL, c) Hemoglobin < 9.0g/dL, unless due to involvement of BM by CLL.
13. Known or suspected hypersensitivity to components of investigational product (in particular, known hypersensitivity or anaphylactic reactions to murine
antibodies or proteins).
14. Life expectancy less than 6 months.
15. Patients known or suspected of not being able to comply with a study protocol.
16. Pregnant or breast feeding patients.
17. Male and female patients with reproductive potential not willing to use effective method of contraception (oral contraceptives, intrauterine device or barrier method of
contraception in conjunction with spermicidal jelly or surgically sterile) during study and 1 year after last dose of study medication.
18. Patients unable to provide informed consent.
19. Patients with severe autoimmune cytopenia as assessed by the physician (Coombs positive patients without clinical signs of autoimmune hemolytic anemia are eligible for study ent

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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