Venetoclax, Rituximab and Ibrutinib in TN Patients With CLL Undetectable Minimal Residual Disease (uMRD) in Treatment-naïve Patients With Chronic Lymphocytic Leukemia (CLL)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Venetoclax, Rituximab, Ibrutinib.
- Who it may be relevant to
- Registry conditions: Chronic Lymphocytic Leukemia (CLL). Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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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)
Overview
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.
Interventions
- Drug Venetoclax
VENETOCLAX: Ramp-up than 400 mg QD - Drug Rituximab
RITUXIMAB: Cycle 7 Day 1 375 mg/m2; Cycles 8-12 Day 1 500 mg/m2 - Drug Ibrutinib
IBRUTINIB 420 mg QD
Primary outcome measures
- uMRD (<10-4) by 6-color flow cytometry in the bone marrow [Time frame: 27 months]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
- 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)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Italy · 1 center
- IRCCS Ospedale San Raffaele — Milan
Identifiers
NCT: NCT04758975 · PS-CLL-009