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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03455517
Other study ID # LLC1518
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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
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