Chronic Lymphocytic LeukemiaPhase 4LymBIONCT04790045
Lymph Node Microenvironment Modifications in Patients With CLL Treated With Venetoclax-based Regimens
A Phase 4 study testing Venetoclax in people with Chronic Lymphocytic Leukemia, run by Paolo Ghia.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Venetoclax
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2023to 31 Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- CLL diagnosis
- Patients receiving treatment with venetoclax-based regimens
- Baseline platelet value >100x109/l
- PT INR and aPTT within normal range
Who cannot join
- Patients receiving anticoagulant or antiplatelet treatment that cannot be safely interrupted before the biopsy
About this study
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:
Read more
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.
Read the detailed 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
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Venetoclax
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Also called core-needle biopsy
Core-needle biopsy to be performed before starting treatment in patients candidates to venetoclax-based regimens
| Study group | Role | What they receive |
|---|---|---|
| Venetoclax-based treatment | Other | Single-arm study Patients enrolled will be receiving venetoclax-based regimens according to the standard of care Receives: Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2021
- Study start1 Nov 2023 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Paolo Ghia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Paolo Ghia, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04790045
- Sponsor's protocol ID
- PS-CLL-005
- Acronym
- LymBIO
- Status last verified
- Oct 2023
- First submitted
- 28 Feb 2021
- Last updated
- 3 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lymph Node Microenvironment Modifications in Patients With CLL Treated With Venetoclax-based Regimens
- ClinicalTrials.gov ID
- NCT04790045
- Acronym / sponsor ID
- LymBIO / PS-CLL-005
- Conditions
- Chronic Lymphocytic Leukemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Paolo GhiaUniversity, hospital or other
- Study start
- 1 Nov 2023 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 10 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Venetoclax-based treatment | Other | Drug: VenetoclaxSingle-arm study Patients enrolled will be receiving venetoclax-based regimens according to the standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- CLL diagnosis
- Patients receiving treatment with venetoclax-based regimens
- Baseline platelet value >100x109/l
- PT INR and aPTT within normal range
Key exclusion criteria (1 listed)
- Patients receiving anticoagulant or antiplatelet treatment that cannot be safely interrupted before the biopsy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenetoclaxAlso: core-needle biopsyCore-needle biopsy to be performed before starting treatment in patients candidates to venetoclax-based regimens | Drug | Venetoclax-based treatment |
Primary outcome
To evaluate lymph node changes in CLL patients treated with venetoclax-based regimens both at molecular level
Time frame: 24 months
Gene expression profile of CLL cells derived from lymph nodes of patients treated with venetoclax-based regimens
To evaluate lymph node changes in CLL patients treated with venetoclax-based regimens both at ultrasound level
Time frame: 24 months
Ultrasound characteristics of lymph nodes of patients treated with venetoclax-based regimens
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2023.
- Individual participant dataSharing planned: No
Related trials for Chronic Lymphocytic Leukemia
RecruitingPhase 2
Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma
Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid Leukemia
RecruitingPhase 2
A Randomized Phase II Study Of Bruton Tyrosine Kinase Inhibitor With Or Without Venetoclax In Veterans With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
RecruitingPhase 1
Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies
Malignancy, Hematologic, Neoplasms, Hematologic
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Venetoclax in people with Chronic Lymphocytic Leukemia, run by Paolo Ghia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate lymph node changes in CLL patients treated with venetoclax-based regimens both at molecular level (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2023.