Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT04790045 |
Other study ID # |
PS-CLL-005 |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
November 1, 2023 |
Est. completion date |
December 31, 2026 |
Study information
Verified date |
October 2023 |
Source |
IRCCS San Raffaele |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
Description:
LN, PB and BM mononuclear cells collected from CLL patients at specified timepoints will be
tested by:
- High-throughput ex vivo drug assay (2D platforms)
- Global transcriptome analysis by RNA sequencing
- Flow cytometry including activation and adhesion/migration markers, e.g. CD69, CD80,
CD86, HLA-DR, CD38, CD49d, CXCR4;
- Phospho-flow assays, to assess the phosphorylation state of proteins involved in BCR
signaling transduction, e.g. AKT and ERK;
- Western blot of nuclear lysates and cytoplasmic protein fractions to validate the
expression of relevant genes
- Targeted deep-sequencing by a previously validated panel
Minimal residual disease evaluation will be performed by:
- 6-color flow cytometry
- NGS CfDNA will be analysed by targeted NGS.
The following features will be evaluated by tailored ultrasound:
Superficial nodal sites (linear probe 7.5 MHz):
- Site
- Size: long and short diameter (sensitivity <5 mm)
- Shape
- Border
- echo-structure of the cortex; assessment of possible intranodal reticulation
- Echogenic description of the hilum: presence, absence and irregular echo-morphology
Optional parameters:
- Doppler evaluation: vascular distribution, vascular resistance
- Contrast enhanced ultrasound (CEUS): 7.5 MHz linear probe (optional);Quantitative
assessment with dedicated software (wash-in and wash-out curves): optional
Deep nodal sites (probe 3.5-5 MHz):
- Site
- Presence/absence of deep lymphoadenopathies
- Size (sensitivity <5 mm)
- Echo-structure of the cortex (only if superficial, e.g. external iliac LN)
Optional parameters:
- Vascular pattern by: color doppler, two-dimensional power doppler and MicroV (only if
superficial, e.g. external iliac LN)
- Contrast enhanced ultrasound (CEUS) (optional): vascular pattern present vs absent,
intensity
Spleen:
- Size (dedicated software to more precisely define the bipolar diameter) : in cm
- Cross sectional area in cm2
Optional parameters:
- Splenic artery resistive index
- Portal vein flow (forward or non-forward portal flow): Vmax ("maximum velocity expressed
in cm" and "mean Velocity expressed in cm")
- Splenic stiffness (with Fibroscan or point share wave or share wave 2D) expressed in kPa
Liver:
- Size
- Echo-structure
Optional parameters:
- Portal vein flow parameters
- Liver artery resistive index
- Liver stiffness expressed in kPa