A Study to Customize Ibrutinib Treatment Regimens for Participants With Previously Untreated Chronic Lymphocytic Leukemia (TAILOR)

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 2

Conditions: Small Lymphocytic Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell

Treatments: Drug: Venetoclax; Drug: Ibrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05963074

2023-504044-34-00 (Registry Identifier)

54179060CLL2032 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of ibrutinib + venetoclax (I+V) and ibrutinib monotherapy regimens in which dosing of ibrutinib is either proactively reduced or reactively modified in response to adverse events (AEs).

Enrollment: 320 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) as per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 diagnostic criteria
• For ibruinib + venetocIax (I+V) cohorts: eastern cooperative oncology group (ECOG) performance status of 0-1. For ibrutinib monotherapy cohorts: ECOG performance status of 0-2
• Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node greater than and equal to (>=) 1.5 centimeters (cm) in longest diameter
• A participant using oral contraceptives must use an additional contraceptive method
• A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or until 1 month after last dose or per local label if more conservative (for example, 3 months in European Union or Canada and 1 month in United States)

Exclusion criteria

• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura, such as those participants with a declining hemoglobin level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of study treatment, or the need for prednisone greater than (>) 20 milligrams (mg) daily (or corticosteroid equivalent) to treat or control the autoimmune disease
• Known bleeding disorders (example, von Willebrand's disease or hemophilia)
• Stroke or intracranial hemorrhage within 6 months prior to enrollment
• Known or suspected Richter's transformation or central nervous system (CNS) involvement
• Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class II, III, or IV congestive heart failure as defined by the New York Heart Association Functional Classification

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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320 participants in 4 patient groups

Cohort 1a: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax

Experimental group

Description:

Participants will receive ibrutinib 420 milligrams (mg) capsule every day (QD) for a lead-in of 3 cycles (1 cycle = 28 days). From Cycle 4, venetoclax 400 mg tablet dose ramp-up (from 20 to 400 mg over 5 weeks) will begin, and venetoclax 400 mg QD will be administered with ibrutinib 420 mg QD, orally for 12 cycles through Cycle 15.

Treatment:

Drug: Ibrutinib

Drug: Venetoclax

Cohort 1b: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax

Experimental group

Description:

Participants will receive ibrutinib 420 mg capsule QD for a lead-in of 3 cycles (1 cycle = 28 days). From Cycle 4, venetoclax 400 mg tablet dose ramp-up (from 20 to 400 mg over 5 weeks) will begin and ibrutinib dose will be reduced to 280 mg and will be administered QD, venetoclax 400 mg tablets QD will be administered with ibrutinib 280 mg for 12 cycles through Cycle 15.

Treatment:

Drug: Ibrutinib

Drug: Venetoclax

Cohort 2a: Continuous Ibrutinib Monotherapy

Experimental group

Description:

Participants will receive ibrutinib 420 mg QD (or last tolerated dose) until disease progression (PD) or unacceptable toxicity.

Treatment:

Drug: Ibrutinib

Cohort 2b: Continuous Ibrutinib Monotherapy

Experimental group

Description:

Participants will receive ibrutinib 420 mg QD for 1 cycle (1 cycle = 28 days) followed by Ibrutinib 280 mg QD (or last tolerated dose) and continue until disease progression or unacceptable toxicity.

Treatment:

Drug: Ibrutinib