Clinical trial NCT03766763: Preemptive Therapy for High Risk Chronic Lymphoid Leukemia Stage a
Official title: Preemptive Therapy with Venetoclax for High Risk Chronic Lymphoid Leukemia Stage a Patients, a Phase II Trial of the FILO
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphoid Leukemia
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
First posted: 2018-12-06
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Open label, single arm, multicenter phase II trial.

Detailed description: Preemptive therapy with Venetoclax for high risk stage A Chronic Lymphoid Leukemia patients, a phase II trial of the FILO group.

PREVENE (PREemptive VENEtoclax) trial.

Eligibility criteria: Inclusion Criteria:

* Established diagnosis of Chronic Lymphoid Leukemia by International Workshop Chronic Lymphoid Leukemia 2008 criteria with Matutes score Superior to 3, or Matutes score egal to 3 with CD200 positive and CD20 low
* High risk Binet stage A, patients presenting at least 2 from 3 risk factors: Lymphocytosis Superior to 13 Giga per liter, CD38 positive, beta2 microglobulin Superior to 2.5 milligram per liter.

Only patients with unmutated status will be treated and followed according to the trial.

* No prior chemotherapy, radiation or antibody treatment
* Age Superior to 18 years
* Life expectancy Superior to 6 months
* Performance status 0 to 2
* All parameters for risk stratification present
* Possibility of follow-up
* Adequate hepatic function per local laboratory reference range as follows: Aspartate transaminase and alanine transaminase Superior to 3.0 of upper limit of normal and Bilirubin inferior or egal to 1.5 of upper limit of normal (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) 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

Exclusion Criteria:

* Binet Stage A patients with progressive disease according to International Workshop Chronic Lymphoid Leukemia 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 Chronic Lymphoid Leukemia 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 Human Immunodeficiency Virus
* Evidence of other clinically significant uncontrolled conditions
* 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
* 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 inhibitors, moderate or strong cytochrome P450 3A inducers
* 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, star fruit.
* Prior and concomitant therapy
* 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
* Not affiliated to social security

Primary outcomes:
measure: Complete response rate
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens
city: Angers
country: France
facility: Chu Angers
city: Annecy
country: France
facility: Ch Annecy
city: Bayonne
country: France
facility: Ch Cote Basque
city: Besançon
country: France
facility: Hopitaljean Minjoz
city: Blois
country: France
facility: CH BLOIS
city: Bordeaux
country: France
facility: Institut Bergonie
city: Béziers
country: France
facility: Ch Beziers
city: Caen
country: France
facility: CHU CAEN
city: Cesson-Sévigné
country: France
facility: Hôpital Privé Sévigné
city: Clermont-Ferrand
country: France
facility: Chu Estaing
city: Créteil
country: France
facility: Chu Creteil
city: Grenoble
country: France
facility: Chu Grenoble
city: La Roche-sur-Yon
country: France
facility: Chd Vendee
city: Le Mans
country: France
facility: Chd Le Mans
city: Lille
country: France
facility: Hopital Huriez
city: Lyon
country: France
facility: Centre leon berard
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Metz
country: France
facility: Centre Hospitalier Regional Metz Thionville
city: Pessac
country: France
facility: Bordeaux Pessac
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Centre Henri Becquerel - Service Hématologie Clinique
city: Tours
country: France
facility: Hôpital Bretonneau - Hématologie et Thérapie Cellulaire
Study officials:
affiliation: French Innovative Leukemia Organisation
name: Vincent LEVY, MD PD
role: PRINCIPAL_INVESTIGATOR
affiliation: French Innovative Leukemia Organisation
name: Luc-Matthieu FORNECKER, MD
role: STUDY_CHAIR
References: