Chronic lymphoid leukemia
Conditions
Interventions
Sponsors
FILO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Established diagnosis of CLL by IWCLL 2008 criteria with Matutes score > 3, or Matutes score = 3 with CD200 positive and CD20 low. • High risk Binet stage A, i.e. patients presenting at least 2 from 3 risk factors ? -Lymphocytosis > 13 G/L ? -CD38 + ? -beta2 microglobulin > 2.5 mg/L. Only patients with unmutated status will be treated and followed according to the trial. • No prior chemotherapy, radiation or antibody treatment. • Age > 18 years. • Life expectancy > 6 months. • ECOG performance status 0 – 2. • All parameters for risk stratification present. • Possibility of follow-up. • Adequate hepatic function per local laboratory reference range as follows: ? -Aspartate transaminase (AST) and alanine transaminase (ALT) =65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: • Binet Stage A patients with progressive disease according to IWCLL 2008 criteria • Clinically apparent autoimmune cytopenia, in particular antiglobulin test positive hemolytic anemia (positive antiglobulin test without anemia is not an exclusion criteria) • Active secondary malignancy or chemotherapy/radiotherapy for any neoplastic disease other than CLL prior to the study • Medical condition requiring the long-term (estimated to be more than one month) use of oral corticosteroids • Patient refusal to perform the bone marrow biopsy for evaluation points • Patients with active bacterial, viral or fungal infection • Subject is known to be positive for HIV. (HIV testing is not required.) • Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: ? -Uncontrolled and/or active systemic infection (viral, bacterial or fungal). ? -Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate. • Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study. • A female patient who is pregnant or breast-feeding. • Concurrent severe diseases which exclude the administration of therapy. ? -heart insufficiency NYHA grade III/IV, LEVF < 50% and or RF <30%, myocardial infarction within the past 6 months prior to study. ? -severe chronic obstructive lung disease with hypoxemia. ? -severe diabetes mellitus. ? -hypertension difficult to control. ? -impaired renal function with creatinine clearance < 50 ml/min according the formula of Cockroft and Gault. • Richter’s syndrome. • Treatment with any of the following within 7 days prior to the first dose of study drug: ? -Steroid therapy for anti-neoplastic intent. ? -moderate or strong cytochrome P450 3A (CYP3A) inhibitors (see Appendix 6 for examples). ? -moderate or strong CYP3A inducers (see Appendix 6 for examples). • Administration or consumption of any of the following within 3 days prior to the first dose of study drug: ? -grapefruit or grapefruit products. ? -Seville oranges (including marmalade containing Seville oranges). ? -star fruit. • Prior and concomitant therapy (see appendix 6). • Malabsorption syndrome or other condition that precludes enteral route of administration • Received a live viral vaccination within 6 months prior to the first dose of study drug. • A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect the patient’s participation in this study or interpretation of study outcomes. • Major surgery within 30 days prior to the first dose of study treatment. • History of prior other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following: ? -Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study. ? -Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which patient is disease-free for = 5 years without further treatm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of Venetoclax in high risk stage A CLL patients;Secondary Objective: •To asses the safety of Venetoclax in high risk stage A CLL patients. •To assess the efficacy of Venetoclax in high risk stage A patients as measured by the overall response rate (ORR) at month 12 and 24. •To assess the proportion of responding patients (PR or CR) with bone marrow MRD > 0.01% at M12 achieving a bone marrow MRD < 0.01% at M24. •To asses the proportion of patients who will be able to stop the treatment at M18 after having achieved a CR with MRD < 0.01% in bone marrow at M12. •To assess the overall survival (OS). •To asses the progression-free survival (PFS). •To assess the event-free survival (EFS). •To assess the Time To Next Treatment (TTNT). •To assess the duration of response (DOR). •Quality of life.;Primary end point(s): Complete response rate (according to IWCLL 2008 guidelines) with MRD < 0.01% (as determined by 8-color technique) in bone marrow at month 12.;Timepoint(s) of evaluation of this end point: At month 12 after treatment start | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Adverse events (AEs), serious adverse events (SAEs) and proportion of patient stopping the treatment for toxicity. • ORR (according to IWCLL 2008 guidelines) at M12 and M24. • Bone marrow MRD at M24 for responding patients with bone marrow MRD > 0.01% at M12. • Proportion of patients in CR with bone marrow MRD < 0.01% at M12 stopping treatment at M18 according to protocole criteria. • Overall survival (OS), defined as time from entry on study to date of death or the last date the patient is known to be alive. • Progression free survival (PFS), defined as time from entry on study to documented progression or death, or the last date the patient is known to be alive and progression-free if progression or death is not observed. • Event-free survival (EFS), defined as time from entry on study to disease recurrence or progression or permanent treatment discontinuation due to toxicity or death. • Time to next treatment (TTNT), defined as time from the end of treatment evaluated in the trial to the next treatment. • Duration of response (DOR), defined as the time from documentation of response to disease progression. • Quality of life according to EQ-5D™. ;Timepoint(s) of evaluation of this end point: - At month 12 after treatment start, then at month 18 and month 24 - Toxicity evaluation during all the study | — |
Countries
France
Contacts
Public ContactDelphine NOLLET
FILO
Outcome results
None listed