Chronic Lymphocytic Leukemia (CLL)Phase 2VALUABLENCT04758975
Venetoclax, Rituximab and Ibrutinib in TN Patients With CLL Undetectable Minimal Residual Disease (uMRD) in Treatment-naïve Patients With Chronic Lymphocytic Leukemia (CLL)
A Phase 2 study testing Venetoclax, Rituximab and Ibrutinib in people with Chronic Lymphocytic Leukemia (CLL), run by Paolo Ghia at 1 site in Italy.
Trial summary
This is a Phase 2, multicenter, open-label uncontrolled interventional study aimed a determining therapeutic benefits of the addition of ibrutinib to 12 months of venetoclax (single-agent for 6 months then combined with rituximab for additional 6 months) in patients with treatment-naïve CLL based on a MRD-guided… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia (CLL)
- What is being tested?
- Venetoclax, Rituximab and Ibrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteItaly
- Study dates
- 19 Sep 2022to 30 Dec 2027
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years but <65 years
- Active CLL/SLL requiring treatment per iwCLL 2018 criteria
- No previous therapy for CLL/SLL
- Adequate bone marrow function:
- ANC ≥1.0 x 109/L;
- Plt ≥25 x 109/L;
- Hgb ≥8.0 g/dl
Who cannot join
- Any prior therapy used for treatment of CLL or SLL
- History of other malignancies, except in situ carcinoma or malignancy treated with curative intent
- Known or suspected history of Richter's transformation
- Known hypersensitivity to one or more study drugs
- Inadequate renal function: CrCl <30 mL/min
- Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
Show all 11Show fewer
- Requires the use of warfarin or derivatives
- Treatment with any of the following within 7 days prior to the first dose of study drug:
- Steroid therapy for anti-neoplastic intent
- Moderate or strong cytochrome P450 3A (CYP3A) inhibitors (see Appendix G for examples)
- Moderate or strong CYP3A inducers (see Appendix G for examples)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Ospedale San Raffaele
Milan, MI, 20132
Eloise Scarano, MSc, +39022643 ext. 3919, scarano.eloise@hsr.it
Lydia Scarfo, MD, +39022643 ext. 6119, scarfo.lydia@hsr.it
About this study
Official title: Venetoclax and Delayed Rituximab With Ibrutinib Consolidation Aiming at Undetectable Minimal Residual Disease (uMRD) in Treatment-naïve Patients With Chronic Lymphocytic Leukemia (CLL)
This is a Phase 2, multicenter, open-label uncontrolled interventional study aimed a determining therapeutic benefits of the addition of ibrutinib to 12 months of venetoclax (single-agent for 6 months then combined with rituximab for additional 6 months) in patients with treatment-naïve CLL based on a MRD-guided approach. Study treatment will be administered according to the following scheme:
VENETOCLAX: Cycle 1 Day 1-Cycle 1 Day 28 Ramp-up with weekly dose escalation; Cycles 2-12: 400 mg QD RITUXIMAB: Cycle 7 Day 1 375 mg/m2; Cycles 8-12 Day 1 500 mg/m2
Read more
At the end of Cycle 12 the MRD status is checked:
3 consecutive uMRD in PB + 1 uMRD in BM at last assessment treatment discontinuation and follow-up At least 1 MRD+ sample in the last 3 assessments. Venetoclax 400 mg QD until uMRD or up to 24 months or unacceptable toxicity (whichever occurs first) in combination with IBRUTINIB 420 mg QD until uMRD or PD or unacceptable toxicity. Venetoclax will be administered orally once daily (QD) beginning with a dose-titration phase (Ramp-up Period). At Cycle 7 Day 1 rituximab will be added for up to 6 monthly cycles (Cycle 7 Day 1 rituximab 375 mg/m2, Cycles 8-12 Day 1 rituximab 500 mg/m2). At Cycle 12 Day 1, disease status, renal function and risk of bleeding will be assessed. Minimal residual disease (MRD) will be evaluated serially in both PB and, after 3 consecutive uMRD in PB, in BM. All subjects with uMRD (defined as those with MRD level <10-4 in the PB in 3 consecutive assessments and in a BM aspirate) will discontinue venetoclax at the end of Cycle 12 (i.e. Cycle 12 Day 28). All subjects with detectable MRD (defined as those with MRD level in the PB and/or BM >10-4) and patients with stable disease without any contraindications to ibrutinib will start treatment with ibrutinib. Ibrutinib will be administered at the standard dose in CLL (i.e. 420 mg QD). Venetoclax will be administered until confirmed uMRD (3 consecutive uMRD in PB, the last one with concomitant uMRD in BM), unacceptable toxicity or disease progression or for a maximum of 2 years and ibrutinib will be continued until unacceptable toxicity, confirmed uMRD or disease progression.
- Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Being tested
- Venetoclax, Rituximab, Ibrutinib
- 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
VENETOCLAX: Ramp-up than 400 mg QD
RituximabDrug
RITUXIMAB: Cycle 7 Day 1 375 mg/m2; Cycles 8-12 Day 1 500 mg/m2
IbrutinibDrug
IBRUTINIB 420 mg QD
| Study group | Role | What they receive |
|---|---|---|
| Venetoclax + Rituximab +/- Ibrutinib | Experimental | VENETOCLAX: Cycle 1 Day 1-Cycle 1 Day 28 Ramp-up with weekly dose escalation; Cycles 2-12: 400 mg QD RITUXIMAB: Cycle 7 Day 1 375 mg/m2; Cycles 8-12 Day 1 500 mg/m2
At the end of Cycle 12 the MRD status is checked:
3 consecutive uMRD in PB + 1 uMRD in BM at last assessment treatment discontinuation and follow-up At least 1 MRD+ sample in the last 3 assessments venetoclax 400 mg QD until uMRD or up to 24 months or unacceptable toxicity (whichever occurs first) in combination with IBRUTINIB 420 mg QD until uMRD or PD or unacceptable toxicity Receives: Drug: Venetoclax; Drug: Rituximab; Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
uMRD (<10-4) by 6-color flow cytometry in the bone marrow
uMRD (<10-4) by 6-color flow cytometry in the bone marrow as best response at any time during treatment for up to 3 months after completion of combined therapy (VR or VR followed by VI)
Measured: 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2021
- Study start19 Sep 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic Leukemia (CLL)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 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
- NCT04758975
- Sponsor's protocol ID
- PS-CLL-009
- Acronym
- VALUABLE
- Status last verified
- Oct 2023
- First submitted
- 11 Feb 2021
- Last updated
- 4 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 4 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Venetoclax and Delayed Rituximab With Ibrutinib Consolidation Aiming at Undetectable Minimal Residual Disease (uMRD) in Treatment-naïve Patients With Chronic Lymphocytic Leukemia (CLL)
- ClinicalTrials.gov ID
- NCT04758975
- Acronym / sponsor ID
- VALUABLE / PS-CLL-009
- Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Paolo GhiaUniversity, hospital or other
- Study start
- 19 Sep 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 17 Feb 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.
This is a Phase 2, multicenter, open-label uncontrolled interventional study aimed a determining therapeutic benefits of the addition of ibrutinib to 12 months of venetoclax (single-agent for 6 months then combined with rituximab for additional 6 months) in patients with treatment-naïve CLL based on a MRD-guided approach. Study treatment will be administered according to the following scheme:
VENETOCLAX: Cycle 1 Day 1-Cycle 1 Day 28 Ramp-up with weekly dose escalation; Cycles 2-12: 400 mg QD RITUXIMAB: Cycle 7 Day 1 375 mg/m2; Cycles 8-12 Day 1 500 mg/m2
At the end of Cycle 12 the MRD status is checked:
3 consecutive uMRD in PB + 1 uMRD in BM at last assessment treatment discontinuation and follow-up At least 1 MRD+ sample in the last 3 assessments. Venetoclax 400 mg QD until uMRD or up to 24 months or unacceptable toxicity (whichever occurs first) in combination with IBRUTINIB 420 mg QD until uMRD or PD or unacceptable toxicity. Venetoclax will be administered orally once daily (QD) beginning with a dose-titration phase (Ramp-up Period). At Cycle 7 Day 1 rituximab will be added for up to 6 monthly cycles (Cycle 7 Day 1 rituximab 375 mg/m2, Cycles 8-12 Day 1 rituximab 500 mg/m2). At Cycle 12 Day 1, disease status, renal function and risk of bleeding will be assessed. Minimal residual disease (MRD) will be evaluated serially in both PB and, after 3 consecutive uMRD in PB, in BM. All subjects with uMRD (defined as those with MRD level <10-4 in the PB in 3 consecutive assessments and in a BM aspirate) will discontinue venetoclax at the end of Cycle 12 (i.e. Cycle 12 Day 28). All subjects with detectable MRD (defined as those with MRD level in the PB and/or BM >10-4) and patients with stable disease without any contraindications to ibrutinib will start treatment with ibrutinib. Ibrutinib will be administered at the standard dose in CLL (i.e. 420 mg QD). Venetoclax will be administered until confirmed uMRD (3 consecutive uMRD in PB, the last one with concomitant uMRD in BM), unacceptable toxicity or disease progression or for a maximum of 2 years and ibrutinib will be continued until unacceptable toxicity, confirmed uMRD or disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Venetoclax + Rituximab +/- Ibrutinib | Experimental | Drug: Venetoclax, Drug: Rituximab, Drug: IbrutinibVENETOCLAX: Cycle 1 Day 1-Cycle 1 Day 28 Ramp-up with weekly dose escalation; Cycles 2-12: 400 mg QD RITUXIMAB: Cycle 7 Day 1 375 mg/m2; Cycles 8-12 Day 1 500 mg/m2 At the end of Cycle 12 the MRD status is checked: 3 consecutive uMRD in PB + 1 uMRD in BM at last assessment treatment discontinuation and follow-up At least 1 MRD+ sample in the last 3 assessments venetoclax 400 mg QD until uMRD or up to 24 months or unacceptable toxicity (whichever occurs first) in combination with IBRUTINIB 420 mg QD until uMRD or PD or unacceptable toxicity |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥18 years but <65 years
- Active CLL/SLL requiring treatment per iwCLL 2018 criteria
- No previous therapy for CLL/SLL
- Adequate bone marrow function:
Key exclusion criteria (11 listed)
- Any prior therapy used for treatment of CLL or SLL
- History of other malignancies, except in situ carcinoma or malignancy treated with curative intent
- Known or suspected history of Richter's transformation
- Known hypersensitivity to one or more study drugs
- Inadequate renal function: CrCl <30 mL/min
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 |
|---|---|---|
| VenetoclaxVENETOCLAX: Ramp-up than 400 mg QD | Drug | Venetoclax + Rituximab +/- Ibrutinib |
| RituximabRITUXIMAB: Cycle 7 Day 1 375 mg/m2; Cycles 8-12 Day 1 500 mg/m2 | Drug | Venetoclax + Rituximab +/- Ibrutinib |
| IbrutinibIBRUTINIB 420 mg QD | Drug | Venetoclax + Rituximab +/- Ibrutinib |
Primary outcome
uMRD (<10-4) by 6-color flow cytometry in the bone marrow
Time frame: 27 months
uMRD (<10-4) by 6-color flow cytometry in the bone marrow as best response at any time during treatment for up to 3 months after completion of combined therapy (VR or VR followed by VI)
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 4 Oct 2023.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Venetoclax, Rituximab and Ibrutinib in people with Chronic Lymphocytic Leukemia (CLL), run by Paolo Ghia at 1 site in Italy.
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 7 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Paolo Ghia, MD, PhD (0039022643 ext. 4797, ghia.paolo@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
uMRD (<10-4) by 6-color flow cytometry in the bone marrow (time frame: 27 months). 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 4 Oct 2023.