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Venetoclax, Rituximab and Ibrutinib in TN Patients With CLL Undetectable Minimal Residual Disease (uMRD) in Treatment-naïve Patients With Chronic Lymphocytic Leukemia (CLL)

NCT04758975 · Status: RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 55

Last updated 2023-10-04

No results posted yet for this study

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 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.

Conditions

  • Chronic Lymphocytic Leukemia (CLL)

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

Sponsors & Collaborators

  • Paolo Ghia

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-09-19
Primary Completion
2024-12-31
Completion
2027-12-30

Countries

  • Italy

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04758975 on ClinicalTrials.gov