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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02910583




Registration number
NCT02910583
Ethics application status
Date submitted
20/09/2016
Date registered
22/09/2016

Titles & IDs
Public title
Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)
Scientific title
Phase 2 Study of the Combination of Ibrutinib Plus Venetoclax in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Secondary ID [1] 0 0
2016-002293-12
Secondary ID [2] 0 0
PCYC-1142-CA
Universal Trial Number (UTN)
Trial acronym
Captivate
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ibrutinib
Treatment: Drugs - venetoclax
Treatment: Drugs - Placebo

Experimental: Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax - Participants receive 420 mg of single-agent ibrutinib for first 3 cycles followed by ibrutinib plus venetoclax combination treatment (ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule) for 12 cycles (a cycle is defined by 28 days) or until disease progression or unacceptable toxicity.

Experimental: MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded) - Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase).

Participants with confirmed uMRD are randomized to receive ibrutinib 420 mg orally once daily on a continuous schedule until MRD-positive relapse, disease progression (PD), or unacceptable toxicity.

After MRD-positive relapse or disease progression (PD) by iwCLL criteria, participants can reintroduce 400 mg venetoclax with a 5-week ramp up. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Placebo comparator: MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded) - Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase).

Participants with confirmed uMRD are randomized to receive placebo orally once daily on a continuous schedule until MRD-positive relapse, PD or unacceptable toxicity.

If MRD-positive relapse or PD is confirmed after restaging per iwCLL criteria, participants can first reintroduce oral daily ibrutinib with the option of subsequently reintroducing 400 mg venetoclax with a 5-week ramp up, if subsequent disease relapse per iwCLL criteria occurs after ibrutinib reintroduction. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Experimental: MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label) - Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase).

Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg orally once daily on a continuous schedule until PD or unacceptable toxicity.

In case of confirmed PD after restaging per iwCLL criteria, participants can continue ibrutinib and reintroduce venetoclax treatment. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Experimental: MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label) - Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase).

Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. Venetoclax was allowed for administration up to 2 years cumulatively from first dose started in the pre-randomization phase to last dose in the randomization phase.


Treatment: Drugs: ibrutinib
ibrutinib administered orally once daily (three 140 mg capsules)

Treatment: Drugs: venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.

Treatment: Drugs: Placebo
placebo capsules to match ibrutinib administered orally once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants
Timepoint [1] 0 0
1 year after randomization
Primary outcome [2] 0 0
FD Cohort: Complete Response Rate (CRR; Complete Response/Complete Response With Incomplete Blood Count Recovery [CR/CRi]) Rate
Timepoint [2] 0 0
From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months.
Secondary outcome [1] 0 0
MRD Cohort: CRR (CR/CRi Rate)
Timepoint [1] 0 0
From the first dose of ibrutinib to the first confirmed PD, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
Secondary outcome [2] 0 0
MRD Cohort: Overall Response Rate (ORR)
Timepoint [2] 0 0
From the first dose of ibrutinib to the first confirmed PD, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
Secondary outcome [3] 0 0
MRD Cohort: Duration of Response (DOR) at 42 Months Landmark Time
Timepoint [3] 0 0
From initial documentation of a response until PD or death from any cause, whichever occurs first, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
Secondary outcome [4] 0 0
MRD Cohort: MRD-Negativity Rate
Timepoint [4] 0 0
From randomization date until before any subsequent antineoplastic therapy, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
Secondary outcome [5] 0 0
MRD Cohort: Tumor Lysis Syndrome (TLS) Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)
Timepoint [5] 0 0
Baseline, and last post-baseline value on or prior to venetoclax first dose date (cycle 4 day 1) or, for participants who never received venetoclax, the post-baseline value closest to cycle 4 day 1 (i.e. 84 days after the first dose date of ibrutinib).
Secondary outcome [6] 0 0
MRD Cohort: Kaplan-Meier Estimate of Progression Free Survival (PFS) Rate at 48 Months Landmark Time
Timepoint [6] 0 0
From the first dose of ibrutinib to the first confirmed PD or death, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
Secondary outcome [7] 0 0
MRD Cohort: Kaplan-Meier Estimate of Overall Survival (OS) Rate at 48 Months Landmark Time
Timepoint [7] 0 0
From the first dose of ibrutinib to time of death, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
Secondary outcome [8] 0 0
MRD Cohort: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
Timepoint [8] 0 0
From first dose until 30 days following last dose of study drug. Overall median treatment duration for the MRD cohort was 45.1 months.
Secondary outcome [9] 0 0
FD Cohort: ORR
Timepoint [9] 0 0
From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months.
Secondary outcome [10] 0 0
FD Cohort: DOR at 60 Months Landmark Time
Timepoint [10] 0 0
From initial documentation of a response until PD or death from any cause, whichever occurs first, for a median follow-up of 69.0 months.
Secondary outcome [11] 0 0
FD Cohort: MRD Negativity Rate
Timepoint [11] 0 0
From randomization date until before any subsequent antineoplastic therapy, for a median follow-up of 69.0 months.
Secondary outcome [12] 0 0
FD Cohort: Kaplan-Meier Estimate of PFS Rate at 66 Months Landmark Time
Timepoint [12] 0 0
From the first dose of ibrutinib to the first confirmed PD or death, for an median follow-up of 69.0 months.
Secondary outcome [13] 0 0
FD Cohort: Kaplan-Meier Estimate of OS Rate at 66 Months Landmark Time
Timepoint [13] 0 0
From the first dose of ibrutinib to time of death, for a median follow-up of 69.0 months.
Secondary outcome [14] 0 0
FD Cohort: TLS Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)
Timepoint [14] 0 0
Baseline, and last post-baseline value on or prior to venetoclax first dose date (cycle 4 day 1) or, for participants who never received venetoclax, the post-baseline value closest to cycle 4 day 1 (i.e. 84 days after the first dose date of ibrutinib).
Secondary outcome [15] 0 0
FD Cohort: Percentage of Participants With TEAEs, Treatment-Emergent SAEs, and Discontinuations Due to TEAEs
Timepoint [15] 0 0
From first dose until 30 days following last dose of study drug. Overall median treatment duration for the FD cohort was 13.8 months.
Secondary outcome [16] 0 0
MRD Cohort: Pharmacokinetics (PK) of Ibrutinib When Dosed in Combination With Venetoclax: Observed Maximum Concentration (Cmax)
Timepoint [16] 0 0
Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
Secondary outcome [17] 0 0
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Time to Cmax (Tmax); Time of Last Measurable Concentration (Tlast); Terminal Elimination Half-Life (t1/2,Term)
Timepoint [17] 0 0
Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
Secondary outcome [18] 0 0
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Area Under the Plasma Concentration-Time Curve (AUC) Over the Last 24-hour Dosing Interval (AUC0-24h); AUC From Time Zero to the Time of Last Quantifiable Concentration (AUClast)
Timepoint [18] 0 0
Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
Secondary outcome [19] 0 0
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Terminal Elimination Rate Constant (?z)
Timepoint [19] 0 0
Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
Secondary outcome [20] 0 0
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Apparent Total Clearance at Steady-State (CLss/F)
Timepoint [20] 0 0
Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
Secondary outcome [21] 0 0
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Cmax
Timepoint [21] 0 0
Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
Secondary outcome [22] 0 0
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Tmax
Timepoint [22] 0 0
Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
Secondary outcome [23] 0 0
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: AUC0-24h
Timepoint [23] 0 0
Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
Secondary outcome [24] 0 0
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: CLss/F
Timepoint [24] 0 0
Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

Eligibility
Key inclusion criteria
* Diagnosis of CLL/SLL that meets 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) diagnostic criteria (Hallek et al), with active disease meeting at least 1 IWCLL criteria for requiring treatment.
* Measurable nodal disease by computed tomography (CT)
* Adequate hepatic, and renal function
* Adequate hematologic function
* absolute neutrophil count >750/µL
* platelet count >30,000 /µL
* hemoglobin >8.0 g/dL
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any prior therapy used for treatment of CLL/SLL
* Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects at risk for tumor lysis syndrome (TLS)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/09/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/03/2024
Sample size
Target
Accrual to date
Final
323
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
St George Hospital /ID# 1142-0654 - Kogarah
Recruitment hospital [2] 0 0
Flinders Medical Centre /ID# 1142-0163 - Bedford Park
Recruitment hospital [3] 0 0
Monash Medical Centre /ID# 1142-0556 - Clayton
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre-East Melbourne /ID# 1142-0633 - East Melbourne
Recruitment hospital [5] 0 0
St Vincent's Hospital Melbourne /ID# 1142-0501 - Fitzroy
Recruitment hospital [6] 0 0
Frankston Hospital /ID# 1142-0715 - Frankston
Recruitment hospital [7] 0 0
Austin Health /ID# 1142-0170 - Heidelberg
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment postcode(s) [6] 0 0
3199 - Frankston
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kentucky
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Italy
State/province [11] 0 0
Lombardia
Country [12] 0 0
Italy
State/province [12] 0 0
Genova
Country [13] 0 0
Italy
State/province [13] 0 0
Milano
Country [14] 0 0
Italy
State/province [14] 0 0
Modena
Country [15] 0 0
Italy
State/province [15] 0 0
Novara
Country [16] 0 0
Italy
State/province [16] 0 0
Padova
Country [17] 0 0
Italy
State/province [17] 0 0
Piacenza
Country [18] 0 0
New Zealand
State/province [18] 0 0
Auckland
Country [19] 0 0
New Zealand
State/province [19] 0 0
Canterbury
Country [20] 0 0
New Zealand
State/province [20] 0 0
Manawatu-Wanganui
Country [21] 0 0
Poland
State/province [21] 0 0
Lubelskie
Country [22] 0 0
Poland
State/province [22] 0 0
Malopolskie
Country [23] 0 0
Poland
State/province [23] 0 0
Podkarpackie
Country [24] 0 0
Poland
State/province [24] 0 0
Pomorskie
Country [25] 0 0
Poland
State/province [25] 0 0
Lodz
Country [26] 0 0
Spain
State/province [26] 0 0
Barcelona
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid
Country [28] 0 0
Spain
State/province [28] 0 0
Navarra
Country [29] 0 0
Spain
State/province [29] 0 0
Granada
Country [30] 0 0
Spain
State/province [30] 0 0
Salamanca

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pharmacyclics LLC.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Janssen Research & Development, LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://yoda.yale.edu


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02910583