Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03455517
Recruitment Status : Not yet recruiting
First Posted : March 6, 2018
Last Update Posted : October 22, 2018
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

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.

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: Venetoclax Drug: Rituximab Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 77 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Multicenter, prospective, interventional, single arm study
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : November 2018
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : March 2021


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




Primary Outcome Measures :
  1. Number of patients achieving complete response (CR) [ Time Frame: At 15 months from treatment start, which is the end of treatment ]

Secondary Outcome Measures :
  1. Number of patients achieving response [ Time Frame: At 15 months from treatment start, which is the end of treatment ]
    Overall response rate (ORR)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03455517


Contacts
Layout table for location contacts
Contact: Enrico Crea +39 0670390514 e.crea@gimema.it
Contact: Paola Fazi +39 0670390514 p.fazi@gimema.it

Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
Layout table for investigator information
Study Chair: Roberto Foà Università degli Studi di Roma "Sapienza"
Study Director: Francesca Romana Mauro Università degli Studi di Roma "Sapienza"

Additional Information:
Layout table for additonal information
Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT03455517     History of Changes
Other Study ID Numbers: LLC1518
First Posted: March 6, 2018    Key Record Dates
Last Update Posted: October 22, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
Chronic myeloid leukemia
Umutated IGVH
Disrupted TP53
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, B-Cell
Venetoclax
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents