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

January 3, 2022 updated by: Gruppo Italiano Malattie EMatologiche dell'Adulto

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

77

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Alessandria, Italy
        • Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia
      • Ascoli Piceno, Italy
        • Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia
      • Asti, Italy
        • Asl Di Asti, Ospedali Riuniti - Presidio Ospedaliero Cardinal G. Massaia - Sc Oncologia
      • Bari, Italy
        • Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
      • Bologna, Italy
        • Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia
      • Cagliari, Italy
        • Ao Brotzu, Presidio Ospedaliero A. Businco - Cagliari - Sc Ematologia E Ctmo
      • Catanzaro, Italy
        • Ao Di Catanzaro "Pugliese-Ciaccio", Presidio Ospedaliero "Ciaccio - de Lellis" - Ematologia
      • Cona, Italy
        • Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione
      • Cuneo, Italy
        • Aso S. Croce E Carle - Cuneo - Sc Ematologia
      • Lecce, Italy
        • Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
      • Meldola, Italy
        • I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica
      • Messina, Italy
        • Ao Ospedali Riuniti "Papardo Piemonte" - Po Papardo - Messina - Sc Ematologia
      • Milano, 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
      • Modena, Italy
        • Aou Di Modena - Sc Ematologia
      • Novara, Italy
        • Aou Maggiore Della Carita' Di Novara - Scdu Ematologia
      • Padova, Italy
        • Aou Di Padova - Uo Ematologia
      • Pagàni, Italy
        • Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia
      • Perugia, Italy
        • Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo
      • Piacenza, Italy
        • Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti
      • Ravenna, Italy
        • Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
      • Reggio Calabria, Italy
        • Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia
      • Reggio Emilia, Italy
        • Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
      • Rimini, Italy
        • Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia
      • Roma, Italy
        • Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica
      • Roma, Italy
        • Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia
      • Terni, Italy
        • Ao S. Maria - Terni - Sc Onco Ematologia
      • Torino, 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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Venetoclax
Venetoclax and rituximab association
Drug: Rituximab
Venetoclax and rituximab association

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients achieving response
Time Frame: At 15 months from treatment start, which is the end of treatment
Overall response rate (ORR)
At 15 months from treatment start, which is the end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

  • Study Chair: Roberto Foà, Università degli Studi di Roma "Sapienza"
  • Study Director: Francesca Romana Mauro, Università degli Studi di Roma "Sapienza"

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 31, 2018

Primary Completion (Actual)

September 5, 2021

Study Completion (Anticipated)

August 1, 2023

Study Registration Dates

First Submitted

February 28, 2018

First Submitted That Met QC Criteria

February 28, 2018

First Posted (Actual)

March 6, 2018

Study Record Updates

Last Update Posted (Actual)

January 4, 2022

Last Update Submitted That Met QC Criteria

January 3, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LLC1518

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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