Clinical trial NCT03455517: Activity and Safety of Front-line Venetoclax and Rituximab in Young and Fit Patients With Chronic Lymphocytic Leukemia
Official title: Activity and Safety of Front-linevenetoclax and Rituximab Association (VeRiTAs) in Young and Fit Patients With Chronic Lymphocytic Leukemia (CLL) and Umutated IGVH and/or Disrupted TP53. A Phase 2 Multicenter Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia
Keywords: Chronic myeloid leukemia
Umutated IGVH
Disrupted TP53
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2018-03-06
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multicenter, prospective, interventional, single arm study
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of patients achieving complete response (CR)
timeFrame: At 15 months from treatment start, which is the end of treatment
Secondary outcomes:
measure: Number of patients achieving response
timeFrame: At 15 months from treatment start, which is the end of treatment
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia
city: Ascoli Piceno
country: Italy
facility: Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia
city: Asti
country: Italy
facility: Asl Di Asti, Ospedali Riuniti - Presidio Ospedaliero Cardinal G. Massaia - Sc Oncologia
city: Bari
country: Italy
facility: Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
city: Bologna
country: Italy
facility: Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia
city: Cagliari
country: Italy
facility: Ao Brotzu, Presidio Ospedaliero A. Businco - Cagliari - Sc Ematologia E Ctmo
city: Catanzaro
country: Italy
facility: Ao Di Catanzaro "Pugliese-Ciaccio", Presidio Ospedaliero "Ciaccio - de Lellis" - Ematologia
city: Cona
country: Italy
facility: Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione
city: Cuneo
country: Italy
facility: Aso S. Croce E Carle - Cuneo - Sc Ematologia
city: Lecce
country: Italy
facility: Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
city: Meldola
country: Italy
facility: I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica
city: Messina
country: Italy
facility: Ao Ospedali Riuniti "Papardo Piemonte" - Po Papardo - Messina - Sc Ematologia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia
city: Milano
country: Italy
facility: Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora
city: Milano
country: Italy
facility: Irccs Ospedale S. Raffaele - Milano - Unità Neoplasie Linfocitarie B
city: Modena
country: Italy
facility: Aou Di Modena - Sc Ematologia
city: Novara
country: Italy
facility: Aou Maggiore Della Carita' Di Novara - Scdu Ematologia
city: Padova
country: Italy
facility: Aou Di Padova - Uo Ematologia
city: Pagàni
country: Italy
facility: Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia
city: Perugia
country: Italy
facility: Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo
city: Piacenza
country: Italy
facility: Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti
city: Ravenna
country: Italy
facility: Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia
city: Reggio Emilia
country: Italy
facility: Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
city: Rimini
country: Italy
facility: Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica
city: Roma
country: Italy
facility: Università degli Studi di Roma "Sapienza"
city: Terni
country: Italy
facility: Ao S. Maria - Terni - Sc Onco Ematologia
city: Torino
country: Italy
facility: Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino
city: Torino
country: Italy
facility: Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2
city: Torino
country: Italy
facility: Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia
Study officials:
affiliation: Università degli Studi di Roma "Sapienza"
name: Francesca Romana Mauro
role: PRINCIPAL_INVESTIGATOR
References: