Patients with refractory/relapsed CLL
Conditions
Interventions
Product Name: ofatumumab
Product Code: Arzerra
Pharmaceutical Form: Solution for infusion
Sponsors
University Hospital Brno
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria: a)Male or female previously treated patients with B-cell CLL requiring therapy according to the revised NCI criteria (including CLL patients with immune-mediated hemolysis or thrombocytopenia). Prior therapy with rituximab (monotherapy or combination therapy) is not necessary. b)Flow cytometry confirmation of CLL immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig at screening. c)Disease recurrence (or refractority) after at least one fludarabine-containing regimen, or after at least two previous chemotherapy regimens without fludarabine; and/or poor marrow reserve not allowing chemotherapy administration (Absolute Neutrophil Count 3 months g)ECOG performance status = 2 h)CT scan performed 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: Subjects meeting any of the following criteria must not be enrolled in an ofatumumab study: a)Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) b)Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study c)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. d)Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy. e)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 f)History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae g)Known HIV positive h)Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. i)Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient. j)Positive serology for Hepatitis B (HBV) 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. See section 10.3.2.1 Hepatitis B screening. k)Positive serology for hepatitis C (HCV) defined as a positive test for anti-HCVAb, in which case reflexively perform a HCV RIBA immunoblot assay on the same sample to confirm the result l)Screening laboratory values: i.creatinine >2.0 times upper normal limit ii.total bilirubin >1.5 times upper normal limit (unless due to CLL involvement of liver or a known history of Gilbert’s disease) iii.ALT >2.5 times upper normal limit (unless due to disease involvement of liver) iv.alkaline phosphatase >2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow) m)Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening. n)Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as intrauterine device, double barrier method or total abstinence. Oral contraceptive pills are not permitted (dexamethasone induces CYP3A4, therefore oral hormonal birth control may be more rapidly or extensively metabolized and, therefore, less effective). o)Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate overall response rate (ORR).;Secondary Objective: The secondary objectives of this study are: 1)To explore the safety profile of the combination of ofatumumab and dexamethasone. 2)To evaluate tumor response parameters: complete response rate (CR); complete response rate with incomplete bone marrow recovery (CRi); partial response rate (PR); and time dependent parameters: progression-free survival (PFS); overall survival (OS). Other/Exploratory Objectives: To explore relevant molecular genetic, immunophenotypic, cytogenetic and pharmacologic markers to identify factors that may be associated with the progression of the CLL, and that can be used to understand response to ofatumumab. ;Primary end point(s): Overall response rate (CR, CRi, PR rates) | — |
Countries
Czech Republic
Outcome results
None listed