Clinical Trials /

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

NCT03455517

Description:

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: LLC1518
  • NCT ID: NCT03455517

Conditions

  • Chronic Myeloid Leukemia

Interventions

DrugSynonymsArms
VenetoclaxVeritas
RituximabVeritas

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
VeritasExperimentalStep 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.
  • Venetoclax
  • Rituximab

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.
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Gruppo Italiano Malattie EMatologiche dell'Adulto

Trial Keywords

  • Chronic myeloid leukemia
  • Umutated IGVH
  • Disrupted TP53

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