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

Chronic Myeloid Leukemia Clinical Trial

— VeRitAs  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03455517
• Other study ID #: LLC1518
• Status: Completed
• Phase: Phase 2
• Start date: October 31, 2018
• Est. completion date: May 11, 2023

Study information

• Verified date: November 2023
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: May 11, 2023
• Est. primary completion date: September 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• Venetoclax
Venetoclax and rituximab association
• Rituximab
Venetoclax and rituximab association

Locations

Country	Name	City	State
Italy	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	Milano
Italy	Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora	Milano
Italy	Irccs Ospedale S. Raffaele - Milano - Unità Neoplasie Linfocitarie B	Milano
Italy	Aou Di Modena - Sc Ematologia	Modena
Italy	Aou Maggiore Della Carita' Di Novara - Scdu Ematologia	Novara
Italy	Aou Di Padova - Uo Ematologia	Padova
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

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients achieving complete response (CR)		At 15 months from treatment start, which is the end of treatment
Secondary	Number of patients achieving response	Overall response rate (ORR)	At 15 months from treatment start, which is the end of treatment

External Links

•   Gimema Foundation