Activity and Safety of Front-line Venetoclax and Rituximab in Young and Fit Patients With Chronic Lymphocytic Leukemia
- Registration Number
- NCT03455517
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 77
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Veritas Venetoclax * 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. Veritas Rituximab * 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.
- Primary Outcome Measures
Name Time Method Number of patients achieving complete response (CR) At 15 months from treatment start, which is the end of treatment
- Secondary Outcome Measures
Name Time Method Number of patients achieving response At 15 months from treatment start, which is the end of treatment Overall response rate (ORR)
Trial Locations
- Locations (31)
Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo
🇮🇹Perugia, Italy
Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica
🇮🇹Roma, Italy
Università degli Studi di Roma "Sapienza"
🇮🇹Roma, Italy
Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti
🇮🇹Piacenza, 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
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
Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
🇮🇹Ravenna, 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
Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione
🇮🇹Cona, Italy
Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
🇮🇹Lecce, Italy
I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica
🇮🇹Meldola, Italy
Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia
🇮🇹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
Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia
🇮🇹Pagàni, 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
Aso S. Croce E Carle - Cuneo - Sc Ematologia
🇮🇹Cuneo, Italy
Ao Ospedali Riuniti "Papardo Piemonte" - Po Papardo - Messina - Sc Ematologia
🇮🇹Messina, Italy
Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora
🇮🇹Milano, Italy
Aou Di Padova - Uo Ematologia
🇮🇹Padova, Italy
Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia
🇮🇹Torino, Italy