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

Primary Purpose

Chronic Myeloid Leukemia

Status
Active
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Venetoclax
Rituximab
Sponsored by
Gruppo Italiano Malattie EMatologiche dell'Adulto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring Chronic myeloid leukemia, Umutated IGVH, Disrupted TP53

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia
  • Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia
  • Asl Di Asti, Ospedali Riuniti - Presidio Ospedaliero Cardinal G. Massaia - Sc Oncologia
  • Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
  • Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia
  • Ao Brotzu, Presidio Ospedaliero A. Businco - Cagliari - Sc Ematologia E Ctmo
  • Ao Di Catanzaro "Pugliese-Ciaccio", Presidio Ospedaliero "Ciaccio - de Lellis" - Ematologia
  • Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione
  • Aso S. Croce E Carle - Cuneo - Sc Ematologia
  • Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
  • I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica
  • Ao Ospedali Riuniti "Papardo Piemonte" - Po Papardo - Messina - Sc Ematologia
  • Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia
  • Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora
  • Irccs Ospedale S. Raffaele - Milano - Unità Neoplasie Linfocitarie B
  • Aou Di Modena - Sc Ematologia
  • Aou Maggiore Della Carita' Di Novara - Scdu Ematologia
  • Aou Di Padova - Uo Ematologia
  • Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia
  • Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo
  • Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti
  • Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
  • Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia
  • Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
  • Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia
  • Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica
  • Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia
  • Ao S. Maria - Terni - Sc Onco Ematologia
  • Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino
  • Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2
  • Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Veritas

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of patients achieving complete response (CR)

Secondary Outcome Measures

Number of patients achieving response
Overall response rate (ORR)

Full Information

First Posted
February 28, 2018
Last Updated
January 3, 2022
Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto
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1. Study Identification

Unique Protocol Identification Number
NCT03455517
Brief Title
Activity and Safety of Front-line Venetoclax and Rituximab in Young and Fit Patients With Chronic Lymphocytic Leukemia
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 31, 2018 (Actual)
Primary Completion Date
September 5, 2021 (Actual)
Study Completion Date
August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia
Keywords
Chronic myeloid leukemia, Umutated IGVH, Disrupted TP53

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Multicenter, prospective, interventional, single arm study
Masking
None (Open Label)
Allocation
N/A
Enrollment
77 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Veritas
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Intervention Description
Venetoclax and rituximab association
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Venetoclax and rituximab association
Primary Outcome Measure Information:
Title
Number of patients achieving complete response (CR)
Time Frame
At 15 months from treatment start, which is the end of treatment
Secondary Outcome Measure Information:
Title
Number of patients achieving response
Description
Overall response rate (ORR)
Time Frame
At 15 months from treatment start, which is the end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roberto Foà
Organizational Affiliation
Università degli Studi di Roma "Sapienza"
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Francesca Romana Mauro
Organizational Affiliation
Università degli Studi di Roma "Sapienza"
Official's Role
Study Director
Facility Information:
Facility Name
Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia
City
Alessandria
Country
Italy
Facility Name
Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia
City
Ascoli Piceno
Country
Italy
Facility Name
Asl Di Asti, Ospedali Riuniti - Presidio Ospedaliero Cardinal G. Massaia - Sc Oncologia
City
Asti
Country
Italy
Facility Name
Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
City
Bari
Country
Italy
Facility Name
Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia
City
Bologna
Country
Italy
Facility Name
Ao Brotzu, Presidio Ospedaliero A. Businco - Cagliari - Sc Ematologia E Ctmo
City
Cagliari
Country
Italy
Facility Name
Ao Di Catanzaro "Pugliese-Ciaccio", Presidio Ospedaliero "Ciaccio - de Lellis" - Ematologia
City
Catanzaro
Country
Italy
Facility Name
Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione
City
Cona
Country
Italy
Facility Name
Aso S. Croce E Carle - Cuneo - Sc Ematologia
City
Cuneo
Country
Italy
Facility Name
Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
City
Lecce
Country
Italy
Facility Name
I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica
City
Meldola
Country
Italy
Facility Name
Ao Ospedali Riuniti "Papardo Piemonte" - Po Papardo - Messina - Sc Ematologia
City
Messina
Country
Italy
Facility Name
Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia
City
Milano
Country
Italy
Facility Name
Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora
City
Milano
Country
Italy
Facility Name
Irccs Ospedale S. Raffaele - Milano - Unità Neoplasie Linfocitarie B
City
Milano
Country
Italy
Facility Name
Aou Di Modena - Sc Ematologia
City
Modena
Country
Italy
Facility Name
Aou Maggiore Della Carita' Di Novara - Scdu Ematologia
City
Novara
Country
Italy
Facility Name
Aou Di Padova - Uo Ematologia
City
Padova
Country
Italy
Facility Name
Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia
City
Pagàni
Country
Italy
Facility Name
Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo
City
Perugia
Country
Italy
Facility Name
Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti
City
Piacenza
Country
Italy
Facility Name
Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
City
Ravenna
Country
Italy
Facility Name
Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia
City
Reggio Calabria
Country
Italy
Facility Name
Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
City
Reggio Emilia
Country
Italy
Facility Name
Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia
City
Rimini
Country
Italy
Facility Name
Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica
City
Roma
Country
Italy
Facility Name
Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia
City
Roma
Country
Italy
Facility Name
Ao S. Maria - Terni - Sc Onco Ematologia
City
Terni
Country
Italy
Facility Name
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 Name
Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2
City
Torino
Country
Italy
Facility Name
Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia
City
Torino
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Links:
URL
http://www.gimema.it
Description
Gimema Foundation

Learn more about this trial

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

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