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).

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

Leukemia, Lymphocytic, Chronic, B-Cell

Chronic Lymphocytic Leukemia

Leukemia

Blood Cancer

Hematologic Neoplasms

Hematologic Malignancies

Hematology

Hematological Malignancies

Small Lymphocytic Lymphoma

Lymphoma

Ibrutinib

Venetoclax

Multicohort Study to Customize Ibrutinib Treatment Regimens for Patients With Previously Untreated Chronic Lymphocytic Leukemia

Best ORR is defined as the percentage of participants who achieve complete remission
(CR), complete remission with an incomplete marrow recovery (CRi), nodular partial
remission (nPR), or partial remission (PR) per International Workshop on Chronic
Lymphocytic Leukemia (iwCLL) 2018 criteria as assessed by investigator.

CR rate is defined as the percentage of participants achieving a best overall response of
CR or CRi per iwCLL 2018 criteria as assessed by investigator.

DOR is defined as the duration in days from the date of initial documentation of PR or
better to the date of first documented evidence of PD or death.

PFS by investigator assessment is defined as the duration from date of randomization to
date of PD or death due to any cause, whichever occurs first.

OS is defined as the time from date of randomization to date of death from any cause.

MRD-negative rate is defined as the percentage of participants who reach MRD-negative
status (that is, less than [<] 1 chronic lymphocytic leukemia (CLL) cell per 10,000
leukocytes or <0.01 percentage [%]) in the peripheral blood.

An adverse event (AE) is any untoward medical occurrence in a participant participating
in a clinical study that does not necessarily have a causal relationship with the
pharmaceutical/biological agent under study.

An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not
necessarily have a causal relationship with the intervention. Severity will be graded
according to the National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death).
Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5=
Death related to adverse event.

Percentage of participants with rate of discontinuation due to AEs will be reported.

Percentage of participants with dose reduction due AEs will be reported.

The adherence rate is defined as the percentage of total dose taken over the total dose
prescribed.

Duration of treatment is defined as the time period in days between the date of first
study treatment administration and date of last administration.

Time to worsening is defined as time interval (months) from randomization to first
observation of deterioration. Time to worsening as measured by EQ-5D-5L will be reported.

Time to worsening is defined as time interval from randomization to first observation of
deterioration. Time to worsening as measured by EORTC QLQ-C30 will be reported.

Time to worsening is defined as time interval from randomization to first observation of
deterioration. Time to worsening as measured by EORTC QLQ-CLL17 will be reported.

Time to Worsening is defined as time interval (months) from randomization to first
observation of deterioration. Time to worsening as measured by FACIT-fatigue total score
will be reported.

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.

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.

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

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.

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).

Best ORR is defined as the percentage of participants who achieve complete remission (CR), complete remission with an incomplete marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria as assessed by investigator.

CR rate is defined as the percentage of participants achieving a best overall response of CR or CRi per iwCLL 2018 criteria as assessed by investigator.

DOR is defined as the duration in days from the date of initial documentation of PR or better to the date of first documented evidence of PD or death.

PFS by investigator assessment is defined as the duration from date of randomization to date of PD or death due to any cause, whichever occurs first.

MRD-negative rate is defined as the percentage of participants who reach MRD-negative status (that is, less than [<] 1 chronic lymphocytic leukemia (CLL) cell per 10,000 leukocytes or <0.01 percentage [%]) in the peripheral blood.

An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

The adherence rate is defined as the percentage of total dose taken over the total dose prescribed.

Duration of treatment is defined as the time period in days between the date of first study treatment administration and date of last administration.

Time to worsening is defined as time interval (months) from randomization to first observation of deterioration. Time to worsening as measured by EQ-5D-5L will be reported.

Time to worsening is defined as time interval from randomization to first observation of deterioration. Time to worsening as measured by EORTC QLQ-C30 will be reported.

Time to worsening is defined as time interval from randomization to first observation of deterioration. Time to worsening as measured by EORTC QLQ-CLL17 will be reported.

Time to Worsening is defined as time interval (months) from randomization to first observation of deterioration. Time to worsening as measured by FACIT-fatigue total score will be reported.

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.

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.

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

Participants will receive ibrutinib 420 mg QD for 3 cycles. Ibrutinib 280 mg QD (or last tolerated dose) will begin at cycle 4 and continue until disease progression or unacceptable toxicity.

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures