Lymph Node Microenvironment Modifications in Patients With CLL Treated With Venetoclax-based Regimens

NCT04790045 | Not Yet Recruiting Phase 4

• 1 other identifier: PS-CLL-005
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

CLL subjects who should receive treatment with a venetoclax-based regimen as per standard of care will be enrolled into this trial, after providing informed consent. The following evaluations will be performed baseline before starting treatment: Baseline assessments: In addition to standard staging procedures before treatment initiation, including blood tests and BM aspirate and biopsy, the following procedures will be performed per protocol:

• Peripheral blood sample drawing for pharmacodynamics studies, MRD assessment and cfDNA evaluation
• Ultrasound-guided lymph node CNB
• Tailored ultrasound evaluation of nodal sites and spleen
• Bone marrow MRD sample drawing (optional) The nodal site for the biopsy will be selected based on the size (the largest nodal lesion will be considered) and the procedure feasibility (only superficial cervical, axillary or inguinal lymph nodes will be considered suitable for biopsy). On treatment assessments: Peripheral blood sampling and ultrasound-guided lymph node CNB will be repeated in patients on venetoclax-based therapy:
• 7 days after completion of venetoclax ramp up phase,
• +12 months after completion of venetoclax ramp-up phase. Patients with residual lymph nodes that are not suitable for ultrasound-guided lymph node CNB will continue the ultrasound monitoring only Patients will follow an intensive ultrasound monitoring schedule, which requires tailored ultrasound evaluation being repeated at the following timepoints:
• 4 weeks after venetoclax ramp-up completion
• Every 2 months thereafter until disease progression or unacceptable toxicity leading to permanent treatment discontinuation. Assessments at progression: A tailored ultrasound of nodal sites and spleen will be performed within 2 weeks from the first signs and/or symptoms of suspected progression. US assessment can be delayed at Investigator's discretion in case pseudo-progression is suspected based on potentially confounding concomitant conditions, e.g. infection. In progressive cases, the same assessments (including BM aspirate and biopsy) will be repeated at the time of disease progression. In patients progressing with bulky lymph nodes an incisional lymph node biopsy (instead of an ultrasound-guided CNB) will be performed to exclude Richter's transformation as per standard of care.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• To evaluate lymph node changes in CLL patients treated with venetoclax-based regimens both at molecular level

  Gene expression profile of CLL cells derived from lymph nodes of patients treated with venetoclax-based regimens

  24 months

• To evaluate lymph node changes in CLL patients treated with venetoclax-based regimens both at ultrasound level

  Ultrasound characteristics of lymph nodes of patients treated with venetoclax-based regimens

  24 months

Study Arms (1)

Venetoclax-based treatment

OTHER

Single-arm study Patients enrolled will be receiving venetoclax-based regimens according to the standard of care

Drug: Venetoclax

Interventions

Venetoclax DRUG

Core-needle biopsy to be performed before starting treatment in patients candidates to venetoclax-based regimens

Also known as: core-needle biopsy

Venetoclax-based treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CLL diagnosis
• Patients receiving treatment with venetoclax-based regimens
• Baseline platelet value \>100x109/l
• PT INR and aPTT within normal range

You may not qualify if:

• \- Patients receiving anticoagulant or antiplatelet treatment that cannot be safely interrupted before the biopsy

Sponsors & Collaborators

• Paolo Ghia: lead

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

venetoclax; Biopsy, Needle

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: February 28, 2021
• First Posted: March 10, 2021
• Study Start: November 1, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 3, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share