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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Oct 2018

Typical duration for phase_2

Geographic Reach

1 country

31 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.5 years study duration

First Submitted

Initial submission to the registry

February 28, 2018

Completed

6 days until next milestone

First Posted

Study publicly available on registry

March 6, 2018

Completed

8 months until next milestone

Study Start

First participant enrolled

October 31, 2018

Completed

2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 5, 2021

Completed

1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 11, 2023

Completed

Last Updated

November 24, 2023

Status Verified

November 1, 2023

Enrollment Period

2.8 years

First QC Date

February 28, 2018

Last Update Submit

November 22, 2023

Conditions

Chronic Myeloid Leukemia

Keywords

Chronic myeloid leukemiaUmutated IGVHDisrupted TP53

Outcome Measures

Primary Outcomes (1)

Number of patients achieving complete response (CR)
At 15 months from treatment start, which is the end of treatment

Secondary Outcomes (1)

Number of patients achieving response
At 15 months from treatment start, which is the end of treatment

Study Arms (1)

Veritas

EXPERIMENTAL

* 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.

Drug: VenetoclaxDrug: Rituximab

Interventions

VenetoclaxDRUG

Venetoclax and rituximab association

Veritas

RituximabDRUG

Venetoclax and rituximab association

Veritas

Eligibility Criteria

Age18 Years - 65 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Gruppo Italiano Malattie EMatologiche dell'Adultolead

Study Sites (31)

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

Alessandria, Italy

Location

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

Location

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

Asti, Italy

Location

Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto

Bari, Italy

Location

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

Bologna, Italy

Location

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

Cagliari, Italy

Location

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

Catanzaro, Italy

Location

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

Cona, Italy

Location

Aso S. Croce E Carle - Cuneo - Sc Ematologia

Cuneo, Italy

Location

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

Lecce, Italy

Location

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

Meldola, Italy

Location

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

Messina, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia

Milan, Italy

Location

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

Milan, Italy

Location

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

Milan, Italy

Location

Aou Di Modena - Sc Ematologia

Modena, Italy

Location

Aou Maggiore Della Carita' Di Novara - Scdu Ematologia

Novara, Italy

Location

Aou Di Padova - Uo Ematologia

Padua, Italy

Location

Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia

Pagàni, Italy

Location

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

Perugia, Italy

Location

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

Piacenza, Italy

Location

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

Ravenna, Italy

Location

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

Reggio Calabria, Italy

Location

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

Reggio Emilia, Italy

Location

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

Rimini, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica

Roma, Italy

Location

Università degli Studi di Roma "Sapienza"

Roma, Italy

Location

Ao S. Maria - Terni - Sc Onco Ematologia

Terni, Italy

Location

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

Torino, Italy

Location

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

Torino, Italy

Location

Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia

Torino, Italy

Location

Related Publications (1)

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.
PMID: 36632738DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

venetoclaxRituximab

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

Francesca Romana Mauro
Università degli Studi di Roma "Sapienza"
PRINCIPAL INVESTIGATOR

Study Design

Study Type: interventional
Phase: phase 2
Allocation: NA
Masking: NONE
Purpose: TREATMENT
Intervention Model: SINGLE GROUP
Sponsor Type: OTHER
Responsible Party: SPONSOR

Study Record Dates

First Submitted

February 28, 2018

First Posted

March 6, 2018

Study Start

October 31, 2018

Primary Completion

September 5, 2021

Study Completion

May 11, 2023

Last Updated

November 24, 2023

Record last verified: 2023-11

Locations

IT(31)

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

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (1)

Study Arms (1)

Veritas

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (31)

Related Publications (1)

Related Links

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

Locations

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (1)

Study Arms (1)

Veritas

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (31)

Related Publications (1)

Related Links

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

Locations