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.
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
Interventions
Drug | Synonyms | Arms |
---|
Venetoclax | | Veritas |
Rituximab | | Veritas |
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
Name | Type | Description | Interventions |
---|
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. | |
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: | Active, not recruiting |
Lead Sponsor: | Gruppo Italiano Malattie EMatologiche dell'Adulto |
Trial Keywords
- Chronic myeloid leukemia
- Umutated IGVH
- Disrupted TP53
Last Updated
October 8, 2020