Back to resultsA Study to Customize Ibrutinib Treatment Regimens for Participants With Previously Untreated Chronic Lymphocytic Leukemia (TAILOR)
Primary Purpose
Leukemia, Lymphocytic, Chronic, B-Cell, Small Lymphocytic Lymphoma
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ibrutinib
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell
Eligibility Criteria
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 within 3 months after the last dose of study treatment 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1a: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax
Cohort 1b: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax
Cohort 2a: Continuous Ibrutinib Monotherapy
Cohort 2b: Continuous Ibrutinib Monotherapy
Arm 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.
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.
Outcomes
Primary Outcome Measures
Best Overall Response Rate (ORR)
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.
Secondary Outcome Measures
Complete Response (CR) Rate
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.
Duration of Response (DOR)
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.
Progression Free Survival (PFS)
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.
Overall Survival (OS)
OS is defined as the time from date of randomization to date of death from any cause.
Cohorts 1a and 1b: Minimal Residual Disease (MRD) Negative Rate
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.
Number of Participants with Adverse Events (AEs)
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.
Number of Participants with AEs by Severity
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
Percentage of participants with rate of discontinuation due to AEs will be reported.
Percentage of Participants with Dose Reduction due AEs
Percentage of participants with dose reduction due AEs will be reported.
Adherence Rates
The adherence rate is defined as the percentage of total dose taken over the total dose prescribed.
Duration of Treatment
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 as Measured by EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L)
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 as Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30)
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 as Measured by EORTC QLQ-CLL17
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 as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score
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.
Full Information
NCT ID
NCT05963074
First Posted
July 19, 2023
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
Collaborators
Pharmacyclics LLC.
1. Study Identification
Unique Protocol Identification Number
NCT05963074
Brief Title
A Study to Customize Ibrutinib Treatment Regimens for Participants With Previously Untreated Chronic Lymphocytic Leukemia
Acronym
TAILOR
Official Title
Multicohort Study to Customize Ibrutinib Treatment Regimens for Patients With Previously Untreated Chronic Lymphocytic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 27, 2023 (Anticipated)
Primary Completion Date
September 29, 2028 (Anticipated)
Study Completion Date
November 22, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
Collaborators
Pharmacyclics LLC.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphocytic, Chronic, B-Cell, Small Lymphocytic Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
320 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1a: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax
Arm Type
Experimental
Arm 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.
Arm Title
Cohort 1b: Ibrutinib Lead-in+Fixed Duration Ibrutinib+Venetoclax
Arm Type
Experimental
Arm 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.
Arm Title
Cohort 2a: Continuous Ibrutinib Monotherapy
Arm Type
Experimental
Arm Description
Participants will receive ibrutinib 420 mg QD (or last tolerated dose) until disease progression (PD) or unacceptable toxicity.
Arm Title
Cohort 2b: Continuous Ibrutinib Monotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
JNJ-54179060, IMBRUVICA
Intervention Description
Ibrutinib capsules will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
VENCLEXTA, VENCLYXTO
Intervention Description
Venetoclax tablets will be administered orally.
Primary Outcome Measure Information:
Title
Best Overall Response Rate (ORR)
Description
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.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Complete Response (CR) Rate
Description
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.
Time Frame
Up to 5 years
Title
Duration of Response (DOR)
Description
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.
Time Frame
Up to 5 years
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
Up to 5 years
Title
Overall Survival (OS)
Description
OS is defined as the time from date of randomization to date of death from any cause.
Time Frame
Up to 5 years
Title
Cohorts 1a and 1b: Minimal Residual Disease (MRD) Negative Rate
Description
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.
Time Frame
Up to 5 years
Title
Number of Participants with Adverse Events (AEs)
Description
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.
Time Frame
Up to 5 years
Title
Number of Participants with AEs by Severity
Description
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.
Time Frame
Up to 5 years
Title
Percentage of Participants with Rate of Discontinuation due to AEs
Description
Percentage of participants with rate of discontinuation due to AEs will be reported.
Time Frame
Up to 5 years
Title
Percentage of Participants with Dose Reduction due AEs
Description
Percentage of participants with dose reduction due AEs will be reported.
Time Frame
Up to 5 years
Title
Adherence Rates
Description
The adherence rate is defined as the percentage of total dose taken over the total dose prescribed.
Time Frame
Up to 5 years
Title
Duration of Treatment
Description
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 Frame
Up to 5 years
Title
Time to Worsening as Measured by EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L)
Description
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 Frame
Up to 5 years
Title
Time to Worsening as Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30)
Description
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 Frame
Up to 5 years
Title
Time to Worsening as Measured by EORTC QLQ-CLL17
Description
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 Frame
Up to 5 years
Title
Time to Worsening as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score
Description
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.
Time Frame
Up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 within 3 months after the last dose of study treatment
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Contact
Phone
844-434-4210
Email
Participate-In-This-Study@its.jnj.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Learn more about this trial
A Study to Customize Ibrutinib Treatment Regimens for Participants With Previously Untreated Chronic Lymphocytic Leukemia
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