Activity and Safety of Front-line Venetoclax and Rituximab in Young and Fit Patients With Chronic Lymphocytic Leukemia

NCT ID: NCT03455517

Last Updated: 2023-11-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-31
• Study Completion Date: 2023-05-11

Brief Summary

Fludarabine, cyclophosphamide, and rituximab (FCR) is the gold treatment for fit and young patients with Chronic Lymphoid Leukemia (CLL). However, patients with a mutation known as IGVH unmutated and patients with a particular characteristic known as 'disrupted TP53' show an inferior outcome after FCR in terms of survival. Venetoclax as a single agent or combined with rituximab is an effective treatment for relapsed/refractory patients with IGVH unmutated CLL and/or del(17p) and is associated with a high rate of clinical responses.

Detailed Description

Fludarabine, cyclophosphamide, and rituximab (FCR) is the gold treatment for fit and young (age ≤65 years) patients with CLL. However, IGVH unmutated patients and patients with disrupted TP53 show an inferior outcome after FCR in terms of PFS and OS. Venetoclax as a single agent or combined with rituximab is an effective treatment for relapsed/refractory patients with IGVH unmutated CLL and/or del(17p) and is associated with a high rate of clinical responses and MRD-negative responses. The achievement of a MRD negative response in CLL is the best treatment endpoint since it is associated with an improved PFS.

In treatment-naive patients with unmutated IGVH and/or disrupted TP53 the venetoclax and rituximab combination could be a more effective regimen than FCR with a 15% increase in the CR rate.

Conditions

Chronic Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Veritas

• Step 1. All patients: venetoclax 5-weeks dose-titration phase with weekly increases in the dose of venetoclax.
• Step 2. All patients will receive 6 courses of the VR combination.
• Step 3. After 6 courses of VR combination:

3a. Patients with no response will be off treatment; 3b. Patients with clinical response (CR or PR) after 6 courses of VR combination will receive venetoclax as a single agent for 6 months. Then, patients will be observed clinically until disease progression or until month 36.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax and rituximab association

Rituximab

Intervention Type: DRUG

Venetoclax and rituximab association

Interventions

Venetoclax

Venetoclax and rituximab association

Intervention Type: DRUG

Rituximab

Venetoclax and rituximab association

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients older than18 years and 65 years or less.
• Diagnosis of CLL meeting the IWCLL 2008 criteria.
• Total CIRS <6, creatinine clearance >30 ml/min [Cockcroft-Gault]) and ECOG performance status of 0-1.
• No prior treatment.
• Umutated IGVH and/or disrupted TP53.
• Active disease meeting at least 1 of the following the IWCLL 2008 criteria for treatment requirement.
• Adequate bone marrow function without transfusion <2 weeks of screening as follows: absolute neutrophil count (ANC) ≥1.0 x 109/L (growth factors administration is allowed); platelets ≥30 x 109/L. If thrombocytopenia due to BM involvement, platelets should be ≥ 30 x 109/L; hemoglobin value ≥8.0 g/dl.
• Adequate renal and hepatic function per local reference laboratory reference ranges
• Female patients of childbearing potential and non-sterile male patients must practice at least one of method of birth control with partner(s) beginning with initial treatment administration and continuing to 12 months after the last dose of Rituximab.
• Male patients must agree to refrain from sperm donation, from initial treatment administration until 12 months after the last dose of Rituximab.
• A signed 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

• Any significant concurrent, uncontrolled medical condition or organ system dysfunction and/or laboratory abnormality or psychiatric disease, which, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk or prevent the subject from signing the informed consent form.
• Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia).
• History of other malignancies Pregnant or lactating females.
• Inadequate renal function: CrCl <30 mL/min.
• Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
• Subject is known to be positive for HIV.
• Evidence of other clinically significant uncontrolled condition(s)
• Prior or concomitant fruits and/or specific drugs.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesca Romana Mauro

Role: PRINCIPAL_INVESTIGATOR

Università degli Studi di Roma "Sapienza"

Locations

Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia

Alessandria, , Italy

Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia

Ascoli Piceno, , Italy

Asl Di Asti, Ospedali Riuniti - Presidio Ospedaliero Cardinal G. Massaia - Sc Oncologia

Asti, , Italy

Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto

Bari, , Italy

Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia

Bologna, , Italy

Ao Brotzu, Presidio Ospedaliero A. Businco - Cagliari - Sc Ematologia E Ctmo

Cagliari, , Italy

Ao Di Catanzaro "Pugliese-Ciaccio", Presidio Ospedaliero "Ciaccio - de Lellis" - Ematologia

Catanzaro, , Italy

Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione

Cona, , Italy

Aso S. Croce E Carle - Cuneo - Sc Ematologia

Cuneo, , Italy

Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia

Lecce, , Italy

I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica

Meldola, , Italy

Ao Ospedali Riuniti "Papardo Piemonte" - Po Papardo - Messina - Sc Ematologia

Messina, , Italy

Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia

Milan, , Italy

Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora

Milan, , Italy

Irccs Ospedale S. Raffaele - Milano - Unità Neoplasie Linfocitarie B

Milan, , Italy

Aou Di Modena - Sc Ematologia

Modena, , Italy

Aou Maggiore Della Carita' Di Novara - Scdu Ematologia

Novara, , Italy

Aou Di Padova - Uo Ematologia

Padua, , Italy

Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia

Pagàni, , Italy

Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo

Perugia, , Italy

Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti

Piacenza, , Italy

Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia

Ravenna, , Italy

Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia

Reggio Calabria, , Italy

Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia

Reggio Emilia, , Italy

Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia

Rimini, , Italy

Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica

Roma, , Italy

Università degli Studi di Roma "Sapienza"

Roma, , Italy

Ao S. Maria - Terni - Sc Onco Ematologia

Terni, , Italy

Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino

Torino, , Italy

Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2

Torino, , Italy

Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia

Torino, , Italy

Countries

Italy

References

Mauro FR, Starza ID, Messina M, Reda G, Trentin L, Coscia M, Sportoletti P, Orsucci L, Arena V, Casaluci GM, Marasca R, Murru R, Laurenti L, Ilariucci F, Stelitano C, Mannina D, Massaia M, Rigolin GM, Scarfo L, Marchetti M, Levato L, Tani M, Arcari A, Musuraca G, Deodato M, Galieni P, Patrizi VB, Gottardi D, Liberati AM, Giordano A, Molinari MC, Pietrasanta D, Mattiello V, Visentin A, Vitale C, Albano F, Neri A, De Novi LA, De Propris MS, Nanni M, Del Giudice I, Guarini A, Fazi P, Vignetti M, Piciocchi A, Cuneo A, Foa R. High rate of durable responses with undetectable minimal residual disease with front-line venetoclax and rituximab in young, fit patients with chronic lymphocytic leukemia and an adverse biological profile: results of the GIMEMA phase II LLC1518 - VERITAS study. Haematologica. 2023 Aug 1;108(8):2091-2100. doi: 10.3324/haematol.2022.282116.

Reference Type: DERIVED

PMID: 36632738 (View on PubMed)

Related Links

http://www.gimema.it

Gimema Foundation

Other Identifiers

LLC1518

Identifier Type: -

Identifier Source: org_study_id