Chronic Lymphocytic Leukaemia
Conditions
Interventions
Product Name: ofatumumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Ofatumumab
Current Sponsor code: GSK1841157
Concentration unit: mg/ml milligram(s)/millilitre
Concentration typ
Sponsors
GlaxoSmithKline Research and Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrollment in the study must meet all of the following criteria: 1. Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig prior to Visit 2 2. Active disease and indication for treatment based on modified IWCLL updated NCI-WG guidelines [Hallek, 2008] defined by presenting at least one of the following conditions: • Evidence of progressive marrow failure as manifested by development of, or worsening of anemia, and/or thrombocytopenia • Massive (i.e., greater than 6 cm below the left costal margin) or progressive or symptomatic splenomegaly • Massive nodes (i.e., greater than 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy • Progressive lymphocytosis with an increase of more than 50% over a 2 month period or 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 more than or equal to 10% within the previous 6 months b. Fevers of greater than 100.5?F (38.0ºC) for 2 or more weeks without other evidence of infection c. Night sweats for more than 1 month without evidence of infection 3. Relapsed CLL: defined as a subject who has received at least one prior CLL therapy and previously achieved a complete or partial remission/response, but after a period of 6 or more months, demonstrate evidence of disease progression [Hallek 2008]. 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 French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. 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
Exclusion criteria: 1. Refractory CLL: defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months of last anti-leukemic therapy [Hallek, 2008] 2. Subjects with platelet count less than 50,000/microliter and ANC less than or equal to 1000/microliter 3. Previous autologous or allogeneic stem cell transplantation 4. Active Autoimmune Hemolytic Anemia (AIHA) requiring corticosteroid therapy greater than 100mg equivalent to hydrocortisone, or chemotherapy 5. Known transformation of CLL (e.g. Richter’s Transformation/syndrome) 6. Known CNS involvement of CLL 7. Chronic or current active 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 8. 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 9. 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 10. History of significant cerebrovascular disease or event with significant symptoms or sequelae 11. Glucocorticoid unless given in doses = 100mg/day hydrocortisone (or equivalent dose of other glucocorticoid) for less than 7 days for exacerbations other than CLL (e.g. asthma) 12. Known HIV positive 13. 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. 14. Screening laboratory values: • Creatinine > 1.5 times upper normal limit (unless normal creatinine clearance) • Total bilirubin > 1.5 times upper normal limit (unless due to liver involvement of CLL) • Alanine Aminotransferase (ALT) > 3.0 times upper normal limit (unless due to liver involvement of CLL) 15. Previous treatment or known or suspected hypersensitivity to ofatumumab 16. 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 17. Subjects known or suspected of not being able to comply with a study protocol 18. 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate progression free survival of combination ofatumumab-fludarabine-cyclophosphamide therapy vs. fludarabine-cyclophosphamide therapy for the treatment of relapsed CLL.;Secondary Objective: Secondary objectives are to evaluate clinical benefit, changes in patient reported outcome (PRO) measures, safety, tolerability and pharmacokinetics of subjects treated with ofatumumab in combination with fludarabine and cyclophosphamide.;Primary end point(s): • Progression free survival (PFS), defined as the interval between randomization until disease progression or death | — |
Countries
Bulgaria, Germany, Greece, Italy, Netherlands, Romania, Spain, United Kingdom
Outcome results
None listed