Chronic Lymphocytic Leukemia MedDRA version: 21.0 Level: LLT Classification code 10009310 Term: CLL System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Gazyvaro
Product Name: obinutuzumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Obinutuzumab
CAS Number: 949142-50-1
Other descriptive name: OBINUTUZUMA
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of symptomatic CLL (according to IWCLL guidelines) • Patients without prior treatment for CLL (Corticoid treatment administered due to necessary immediate intervention is allowed; within the last 10 days before start of study treatment only dose equivalents of maximum 20 mg prednisolone are permitted; • Patients aged = 18 years, not fit for FCR-like regimens, according to the treating physician; • Able to adhere to the study visit schedule and other protocol requirements; • WHO performance status of = 2 • Laboratory test results within these ranges: - absolute neutrophil count = 1.0 x 109/l and, platelet count and = 50 x 109/l unless due to bone marrow infiltration, - creatinine clearance = 45 ml/min .(using 24-hour creatinine clearance or modified Cockcroft-Gault equation - total bilirubin = 1,5 x ULN unless considered due to Gilbert’s syndrome, - transaminases = 3 x ULN; • Negative serum or urine pregnancy test within 28 days prior to registration (all females of childbearing potential); • Written informed consent •Patient is capable of giving informed consent 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: • Current inclusion in other clinical trials • Intolerance of exogenous protein administration; • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products. • Positive hepatitis serology (serology testing required at screening), as follows: -Hepatitis B virus (HBV): Patients with positive serology for hepatitis B defined as positivity for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc). -Hepatitis C virus (HCV): Patients with positive hepatitis C serology unless HCV- (RNA) is confirmed negative. • HIV positive patients; • Active fungal, bacterial, and/or viral infection that requires systemic therapy; Note: active controlled as well as chronice/recurrent infections are at risk of reactivation/infection during teatment with obinutuzumab and/or venetoclax); • Vaccination with a live vaccine a minimum of 28 days prior to registration. • Use of any other experimental drug or therapy within 28 days of baseline; • Concurrent use of other anti-cancer agents or treatments; • History of prior malignancy, except for conditions as listed below if patients have recovered from the acute side effects incurred as a result of previous therapy: -Malignancies surgically treated with curative intent and with no known active disease present for 3 years before randomization -Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease -Adequately treated cervical carcinoma in situ without evidence of disease • Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease) (CTCAE grade III-IV); • Severe pulmonary dysfunction (CTCAE grade III-IV); • Severe neurological or psychiatric disease (CTCAE grade III-IV); • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, hypertension, hyperthyroidism or hypothyroidism etc.) • Women who are pregnant or lactating; • 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 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 18 months after end of antibody treatment and male patients for 6 months after end of treatment. • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To separately study the efficacy, defined as MRD negative bone marrow and no progression according to the IWCLL criteria, of the two arms of the study of either venetoclax maintenance or MRD-guided venetoclax maintenance after sequential regimens of obinutuzumab (pre-induction) followed by 6 cycles obinutuzumab with venetoclax and 6 cycles of venetoclax (induction) in first-line patients with CLL and unfit for FCR-like regimens.;Secondary Objective: - To determine efficacy as assessed by additional outcome measures, including overall response, PFS, event free survival (EFS), OS ; - To determine the impact of the study treatment on quality of life and geriatric scores (including a biological senescence marker of skin biopsy) - Toxicity of venetoclax after pre-induction, especially tumorlysis and neutropenia - To identify predictive factors for response and resistance mechanisms via: - Next-generation sequencing (NGS) at baseline and at progression - Flow-based subset analysis on expression levels of Bcl-2 proteins at baseline, during therapy and at progression - Analyses of malignant and non-malignant immune cells in PB and in LN at baseline and during treatment ;Primary end point(s): •MRD negative bone marrow after maximum 24 cycles of (planned) venetoclax and no progression according to IWCLL criteria at any earlier timepoint.;Timepoint(s) of evaluation of this end point: This endpoint will be evaluated when all relevant data of all patients are available and evaluated | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Efficacy as assessed by additional outcome measures, including overall response, PFS, EFS and OS; • MRD in blood • Toxicity of venetoclax after pre-induction, especially tumorlysis and neutropenia • Quality of life • Geriatric assessment • P16 expression in skin biopsy • Predictive factors for response and resistance mechanisms: -NGS at baseline and at progression -Flow-based subset analysis on expression levels of Bcl-2 proteins at baseline, during therapy and at progression -Analyses of malignant and non-malignant immune cells in PB and in LN at baseline and during treatment ;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated when relevant data for all patients are available and evaluated | — |
Countries
Netherlands
Contacts
Public ContactHOVON Data Center
HOVON
Outcome results
None listed