Chronic Lymphocytic Leukaemia MedDRA version: 19.0 Level: LLT Classification code 10068919 Term: B-cell chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: ofatumumab
Product Code: GSK1841157
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ofatumumab
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrollment in the study must meet all of the following criteria: Adults with documented diagnosis of CLL based on the modified IWCLL updated NCIWG guidelines 1. At least PR according to the revised 2008 NCI-WG CLL criteria within 3 months of the response assessment after the last dose of 2nd/3rd line treatment 2. The anti-leukemic treatment before study entry should have been for at least 3 months or 3 cycles 3. ECOG Performance Status of 0-2 4. 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 155 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 377
Exclusion criteria
Exclusion criteria: 1. Known primary or secondary fludarabine-refractory subjects, defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months 2. Prior maintenance therapy 3. Known transformation of CLL (e.g. Richter’s transformation), prolymphocytic leukemia (PLL), or CNS involvement of CLL 4. Active Autoimmune Hemolytic Anemia (AIHA) requiring treatment except if in the opinion of the investigator it is thought not to affect the subject’s safety, the conduct of the study or the interpretation of the data 5. Previous autologous or allogeneic stem cell transplantation 6. 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 B or C (Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded*.) 7. Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry except if in the opinion of the investigator it is thought not to affect the subject’s safety, the conduct of the study or the interpretation of the data 8. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to screening, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities except if in the opinion of the investigator it is thought not to affect the subject’s safety, the conduct of the study or the interpretation of the data 9. History of significant cerebrovascular disease or event with symptoms or sequelae 10. Significant concurrent, uncontrolled medical condition that in the opinion of the investigator contraindicates participation in this study 11. Other anti-leukemic use of medications including glucocorticoids 12. Known HIV positive 13. Screening laboratory values: • Platelets 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 or Gilbert’s syndrome) • Alanine Aminotransferase (ALT) > 2.5 times upper normal limit (unless due to liver involvement of CLL) • Alkaline phosphatase > 2.5 times upper normal limit 14. Known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator or medical monitor contraindicates study participation 15. Subjects who have received treatment with any non-marketed drug substance or experimental therapy within 5-terminal half-lives or 4 weeks whichever is longer prior to first dose of study medication or currently participating in any other interventional clinical study Note: Participation in any other interven
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate progression free survival (PFS) of ofatumumab maintenance treatment versus no further treatment after remission induction in subjects with relapsed Chronic Lymphocytic Leukaemia (CLL). ; Secondary Objective: ? To evaluate the improvement in response, improvement in response time to next CLL treatment and overall survival in subjects receiving ofatumumab maintenance compared to no further treatment ? To evaluate the PFS after next-line therapy and the time to progression after nextline therapy ? To evaluate the safety and tolerability in subjects with CLL receiving ofatumumab maintenance compared to no further treatment ? To evaluate the health-related quality of life in subjects with CLL receiving ofatumumab maintenance compared to no further treatment as assessed by changes in patient reported outcome (PRO) measures relative to baseline ? To evaluate prognostic marker correlation with clinical response in subjects with CLL receiving ofatumumab maintenance compared to no further treatment ? To evaluate ofatumumab pharmacokinetic parameters in subjects with CLL receiving maintenance ofatumumab every 2 months ;Primary end point(s): The primary endpoint is progression-free-survival which is defined as the time from randomization to the date of disease progression or death due to any cause.; Timepoint(s) of evaluation of this end point: Calculated from entry into the study until the time of disease progression (or death due to any cause). To be evaluated at interim efficacy analysis (events =187 events) and at the time the full number of events are reached (280 events) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: •Improvement in response--- assessed at each visit (every 2 months during study, every 3 months in follow-up) •Time to next treatment—following progressive disease, assessed ~ every 3 months in survival follow-up (at minimum- yearly) •Overall survival-assessed at each visit (e every 2 months during study, every 3 months in follow-up, ~ every 3 months in survival follow-up) until time of death •PFS after next-line treatment- assessed after next CLL treatment at every survival follow-up visit (~ every 3 months) •Changes in PRO measures –assessed at baseline, study visits and follow-up •Changes in PRO scores- assessed at baseline, study visits and follow-up •Improvement of ECOG performance- assessed at baseline, study visits and follow-up ; Secondary end point(s): Secondary Endpoints: Clinical: ? Improvement in response ? Time to next treatment ? Overall survival ? Progression-free survival after next-line therapy ? Time to progression after next-line therapy ? Changes in patient reported outcome (PRO) measures ? Changes in patient reported outcome (PRO) scores ? Improvement of ECOG performance status ? B-symptoms/Constitutional symptoms/fatigue ? Incidences of and number of subjects with grade 3 and 4 infections ? Incidence, severity of adverse events, serious adverse events and other safety parameters ? Evaluation of myelosuppression (anemia, neutropenia, thrombocytopenia) ? Frequency of transfusions ? Incidence of Autoimmune Hemolytic Anemia (AIHA) ? Human Anti Human Antibodies (HAHA) ? IgG, IgA, IgM serum lev | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Denmark, Finland, France, Greece, Hungary, India, Israel, Italy, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Sweden, Turkey, Ukraine, United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed