An open-label, multi-center, three arm randomized, phase III study to compare the efficacy and safety of RO5072759 + chlorambucil (GClb), rituximab + chlorambucil (RClb)or chlorambucil (Clb) alone in previously untreated CLL patients with comorbidities. - CLL11
- Conditions
- Patients with previously untreated B-CLL with comorbidities.MedDRA version: 9.1Level: LLTClassification code 10003946
- Registration Number
- EUCTR2009-012476-28-IT
- Lead Sponsor
- F.Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 781
1. Have documented CD20+ B-CLL according to NCI criteria 2. Previously untreated CLL requiring treatment according to the NCI criteria (Hallek,M; Blood 2008) 3. Total CIRS score >6 (Appendix 3) or creatinine clearance <70 ml/min or both (Appendix 4) 4. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L) and platelets (Plt) ≥ 75 x 109/L unless cytopenia is caused by the underlying disease, i.e. no evidence of additional bone marrow dysfunction (e.g. myelodysplastic syndrome [MDS], hypoplastic bone marrow) 5. Age 18 years or older 6. Life expectancy >6 months 7. Able and willing to provide written informed consent and to comply with the study protocol procedures.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Patients who have received previous CLL therapy 2. Transformation of CLL to aggressive NHL (Richter s transformation) 3. One or more individual organ / system impairment score of 4 as assessed by the CIRS definition 4. Inadequate renal function: Creatinine clearance < 30 ml/min 5. Inadequate liver function: NCICTC Grade 3 liver function tests (AST, ALT >5 x ULN for >2 weeks; Bilirubin >3 x ULN) unless due to underlying disease. 6. Patients with manifest auto-immune haemolytic anemia (AIHA). However, Coombs positive with no clinical signs of AIHA are eligible. 7. History of other malignancy which could affect compliance with the protocol or interpretation of results. Patients with a history of malignancy that has been treated but not with curative intent, will be excluded, unless the malignancy has been in remission without treatment for ≥ 2 years prior to enrolment. 8. Patients with active bacterial, viral, or fungal infection requiring systemic treatment. 9. Patients with known infection with Human immunodeficiency virus (HIV) or Human T Cell Leukemia Virus 1 (HTLV-1). 10. Positive hepatitis serology (see also protocol Section 5.9.2): Hepatitis B (HBV): Patients with positive serology for Hepatitis B defined as positivity for Hepatitis B surface antigen (HBsAg) or anti Hepatitis B core antibody (anti-HBc). Patients positive for anti-HBc may be included if Hepatitis B viral DNA is not detectable. Hepatitis C (HCV): Patients with positive Hepatitis C serology 11. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products. 12. Hypersensitivity to Clb or to any of the excipients 13. Women who are pregnant or lactating 14. Fertile men or women of childbearing potential unless: (1) surgically sterile or ≥ 2 years after the onset of menopause (2) willing to use a highly effective of contraceptive method (Pearl Index <1) such as oral contraceptives, intrauterine device, sexual abstinence or barrier method of contraception in conjunction with spermicidal jelly during study treatment and in female patients for 12 months after end of antibody treatment and male patients for 6 months after end of chlorambucil treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate clinically relevant statistical superiority in progression-free survival (PFS) with GClb compared to RClb and Clb alone and RClb compared to Clb [GClb vs Clb; GClb vs RClb; RClb vs Clb] in previously untreated CLL patients with comorbidities.;Secondary Objective: To evaluate PFS based on IRC To evaluate PFS censoring pts who started new anti-leukemic therapy before showing signs of disease progression To evaluate and compare in each arm: OR rate, CR and PR after the end of treatment, best OR rate achieved during treatment or within 6 m of end of treatment, event-free survival, disease-free survival in CR/CRi patients, and duration of response in CR/CRi and PR pts. Et al.;Primary end point(s): Progression Free Survival (PFS).
- Secondary Outcome Measures
Name Time Method