Preemptive therapy with Venetoclax for high risk CLL stage A patients, a phase II trial of the FILO PREVENE (PREemptive Venetoclax) trial

Phase 1

Conditions: Chronic lymphoid leukemia
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2018-001475-20-FR

Lead Sponsor: FILO

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 82

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) < 3.0 x ULN
?-Bilirubin =1.5 x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin).
•Willingness to accept highly effective methods of contraception for the duration of therapy and 12 months thereafter.
•Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [ß-hCG]) or urine pregnancy test at Screening.
•Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study

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 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

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