A phase III, open label, randomized, multicenter trial of Ofatumumab added to Chlorambucil vs. Chlorambucil Monotherapy in previously untreated patients with Chronic Lymphocytic Leukemia

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 444

Inclusion Criteria

1. Diagnosis of CLL defined by: Circulating lymphocytes ≥5,000/μL for a duration of at least 3 months* AND Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig prior to Visit 2 * CLL might be suspected in otherwise healthy adults who have an absolute increase in B-cells but who have less than 5,000/μL blood lymphocytes (defined as monoclonal B-lymphocytosis, MBL). The presence of a cytopenia caused by a typical marrow infiltrate defines the diagnosis of CLL regardless of the number of peripheral B-lymphocytes or of the lymph node involvement. 2. Active disease and indication for treatment based on modified NCI-WG guidelines [Hallek, 2008] defined by presenting at least any one of the following conditions: Evidence of progressive marrow failure as manifested by development or worsening of anemia and/or thrombocytopenia Massive (i.e. > 6cm below the left costal margin) or progressive or symptomatic splenomegaly Massive nodes (i.e. > 10cm in longest diameter) or progressive or symptomatic lymphadenopathy Progressive lymphocytosis with an increase of more than 50% over a two month period or an lymphocyte doubling time of less than 6 months A minimum of any one of the following disease-related symptoms must be present: a) Unintentional Weight loss ≥ 10% within the previous six months b) Fevers > 100.5F (38.0C) for ≥ 2 weeks without evidence of infection c) Night sweats for more than 1 month without evidence of infection 3. Not been previously treated for CLL (prior autoimmune hemolytic anemia treatment permitted) 4. ECOG Performance Status of 0-2 5. Life expectancy of at least 6 months 6. Age ≥ 18 years 7. Signed written informed consent prior to performing any study-specific 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

Exclusion Criteria

1. Prior immuno- or chemotherapy for CLL with any agent except corticosteroids used to treat autoimmune hemolytic anemia 2. Previous autologous or allogeneic stem cell transplantation 3. Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy > 100mg equivalent to hydrocortisone, or chemotherapy 4. Known transformation of CLL (e.g. Richter) 5. Known CNS involvement of CLL 6. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. 7. Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. 8. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities 9. History of significant cerebrovascular disease or event with significant symptoms or sequelae 10. Glucocorticoid use, unless given in doses ≤ 100mg/day hydrocortisone (or equivalent dose of other glucocorticoid) for <7 days for exacerbations other than CLL (e.g. asthma) 11. Known HIV positive 12. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test will be performed and if positive the subject will be excluded. Note: If HBcAb positive and HBsAb positive, which is indicative of a past infection, the subject can be included. 13. Screening laboratory values: Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance) Total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of CLL) alanine transaminase (ALT) > 3.0 times upper normal limit (unless due to liver involvement of CLL) 14. Previous treatment or known or suspected hypersensitivity to ofatumumab15. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to Visit 1, whichever is longer or currently participating in any other interventional clinical study 16. Known or suspected inability to comply with study protocol 17. Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last treatment dose. Adequate contraception is defined as abstinence, oral hormonal birth control, hormonal birth control injections, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilization if male partner is sole partner for that subject. The double barrier method can be used in regions where considered acceptable and adequate (condom or occlusive cap plus spermicidal agent).