Preemptive Therapy for High Risk Chronic Lymphoid Leukemia Stage a

Phase 2

Active, not recruiting

• Conditions: Chronic Lymphoid Leukemia
• Interventions: Drug: Venetoclax

• Registration Number: NCT03766763
• Lead Sponsor: French Innovative Leukemia Organisation

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.

Study Timeline

• Study First Submitted: 2018-12-05
• Study First Submitted QC: 2018-12-05
• Study First Posted: 2018-12-06
• Study Start: 2019-05-22
• Primary Completion: 2022-01-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-25
• Last Update Posted: 2024-10-29
• Study Completion: 2030-04-24

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 82

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ARM A VENETOCLAX	Venetoclax	VENETOCLAX

Primary Outcome Measures

Name	Time	Method
Complete response rate	12 months	according to International Workshop Chronic Lymphoid Leukemia 2008 guidelines and with Minimal Residual Disease inferior to 0.01 percent (as determined by 8-color technique) in bone marrow at month 12.

Trial Locations

Locations (23)

Chu Amiens; 🇫🇷 Amiens, France

Chu Angers; 🇫🇷 Angers, France

Ch Annecy; 🇫🇷 Annecy, France

Ch Cote Basque; 🇫🇷 Bayonne, France

Hopitaljean Minjoz; 🇫🇷 Besançon, France

CH BLOIS; 🇫🇷 Blois, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Ch Beziers; 🇫🇷 Béziers, France

CHU CAEN; 🇫🇷 Caen, France

Hôpital Privé Sévigné; 🇫🇷 Cesson-Sévigné, France

Chu Estaing; 🇫🇷 Clermont-Ferrand, France

Chu Creteil; 🇫🇷 Créteil, France

Chu Grenoble; 🇫🇷 Grenoble, France

Chd Vendee; 🇫🇷 La Roche-sur-Yon, France

Chd Le Mans; 🇫🇷 Le Mans, France

Hopital Huriez; 🇫🇷 Lille, France

Centre leon berard; 🇫🇷 Lyon, France

Institut Paoli Calmette; 🇫🇷 Marseille, France

Centre Hospitalier Regional Metz Thionville; 🇫🇷 Metz, France

Bordeaux Pessac; 🇫🇷 Pessac, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Centre Henri Becquerel - Service Hématologie Clinique; 🇫🇷 Rouen, France

Hôpital Bretonneau - Hématologie et Thérapie Cellulaire; 🇫🇷 Tours, France