Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL) (Captivate)

Phase 2 Study of the Combination of Ibrutinib Plus Venetoclax in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

This is a multicenter, 2-cohort Phase 2 study assessing both minimal residual disease (MRD)-guided discontinuation and fixed duration therapy with the combination of ibrutinib + venetoclax in subjects with treatment-naïve CLL or SLL.

Study Overview

• Status: Completed
• Conditions: Leukemia; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: ibrutinib; Drug: venetoclax; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 323
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital /ID# 1142-0654
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre /ID# 1142-0163
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre /ID# 1142-0556
    • East Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Centre-East Melbourne /ID# 1142-0633
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne /ID# 1142-0501
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital /ID# 1142-0715
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health /ID# 1142-0170
• Italy
  • Genova, Italy, 16132
    • Ospedale Policlinico San Martino /ID# 1142-0903
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda /ID# 1142-0581
  • Modena, Italy, 41124
    • Azienda Ospedaliero-Universitaria di Modena /ID# 1142-0524
  • Novara, Italy, 28100
    • Azienda Ospedaliero Universitaria Maggiore della Carita di Novara /ID# 1142-0582
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova /ID# 1142-1175
  • Piacenza, Italy, 29121
    • Azienda USL di Piacenza - Ospedale Guglielmo da Saliceto /ID# 1142-1182
  • Lombardia
    • Milan, Lombardia, Italy, 20132
      • Ospedale San Raffaele IRCCS /ID# 1142-0523
• New Zealand
  • Auckland, New Zealand, 0622
    • North Shore Hospital /ID# 1142-0663
  • Auckland
    • Otahuhu, Auckland, New Zealand, 2025
      • Middlemore Hospital /ID# 1142-0662
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Christchurch Hospital /ID# 1142-0589
  • Manawatu-Wanganui
    • Palmerston North, Manawatu-Wanganui, New Zealand, 4414
      • Palmerston North Hospital /ID# 1142-0585
• Poland
  • Lodz, Poland, 93-510
    • Medical Univ. of Lodz and Copernicus Memorial Hospital /ID# 1142-0531
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-081
      • Duplicate_Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie /ID# 1142-0590
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-510
      • Malopolskie Centrum Medyczne /ID# 1142-0364
  • Podkarpackie
    • Brzozow, Podkarpackie, Poland, 36-200
      • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. /ID# 1142-0592
  • Pomorskie
    • Gdańsk, Pomorskie, Poland, 80-952
      • Samodzielny Publiczny Szpital Klinczny Nr-1- Akademickie Cenrum Klinic /ID# 1142-0529
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona /ID# 1142-0533
  • Barcelona, Spain, 08041
    • Hospital Santa Creu i Sant Pau /ID# 1142-0535
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves /ID# 1142-1196
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal /ID# 1142-0874
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 1142-0864
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca /ID# 1142-0790
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Duran i Reynals /ID# 1142-0604
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro, Majadahonda /ID# 1142-0536
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Complejo Hospitalario de Navarra /ID# 1142-1197
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope /ID# 1142-0047
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at UC San Diego /ID# 1142-0241
    • Orange, California, United States, 92868-3201
      • UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1142-0008
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Center /ID# 1142-0071
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey /ID# 1142-1193
  • New York
    • New Hyde Park, New York, United States, 11042
      • Northwell Health/Long Island Jewish Hospital /ID# 1142-0350
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital/Weill Cornell Med College /ID# 1142-0200
    • Rochester, New York, United States, 14642-0001
      • University of Rochester Cancer Center /ID# 1142-0127
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Charlotte-Mecklenberg Hospital, Carolinas Healthcare System, Levine Cancer Inst /ID# 1142-0733
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation /ID# 1142-0739
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania /ID# 1142-0069
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404-1108
      • Tennessee Oncology - Chattanooga /ID# 1142-0123
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center /ID# 1142-0032
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute /ID# 1142-0114

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: ibrutinib; ibrutinib administered orally once daily (three 140 mg capsules); Drug: 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.
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.	Drug: ibrutinib; ibrutinib administered orally once daily (three 140 mg capsules); Drug: 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.
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.	Drug: ibrutinib; ibrutinib administered orally once daily (three 140 mg capsules); Drug: 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.; Drug: Placebo; placebo capsules to match ibrutinib administered orally once daily
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.	Drug: ibrutinib; ibrutinib administered orally once daily (three 140 mg capsules); Drug: 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.
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.	Drug: ibrutinib; ibrutinib administered orally once daily (three 140 mg capsules); Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants	DFS is defined as time from randomization date to MRD-positive relapse, or disease progression per investigator assessment (per 2008 International Workshop for Chronic Lymphocytic Leukemia [IWCLL] criteria [Halleck et al]) or death from any cause, whichever occurred first. 1-year DFS estimated using Kaplan-Meier method at 12 months landmark time.	1 year after randomization
FD Cohort: Complete Response Rate (CRR; Complete Response/Complete Response With Incomplete Blood Count Recovery [CR/CRi]) Rate	CR/CRi rate is defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi) per 2008 IWCLL criteria (halleck et al.) on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurred earlier.	From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	TLS risk reduction was summarized by the percentage of participants with TLS risk reduced from high at baseline to medium or low after ibrutinib lead-in. A reduction in TLS risk from high risk to medium or low risk is clinically meaningful because there is a reduction in the extent of TLS monitoring and risk of hospitalization. TLS risk category is defined as the tumor burden category, where: Low=All lymph nodes (LN) < 5 cm AND absolute lymphocyte count (ALC) < 25 x 10^9/L; Medium=Any LN 5 cm to < 10 cm OR ALC ≥ 25 x 10^9/L; High=Any LN ≥ 10 cm OR ALC ≥ 25 x10^9/L AND any LN ≥ 5 cm.	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).
FD Cohort: TLS Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)	TLS risk reduction was summarized by the percentage of participants with TLS risk reduced from high at baseline to medium or low after ibrutinib lead-in. A reduction in TLS risk from high risk to medium or low risk is clinically meaningful because there is a reduction in the extent of TLS monitoring and risk of hospitalization. TLS risk category is defined as the tumor burden category, where: Low=All lymph nodes (LN) < 5 cm AND absolute lymphocyte count (ALC) < 25 x 10^9/L; Medium=Any LN 5 cm to < 10 cm OR ALC ≥ 25 x 10^9/L; High=Any LN ≥ 10 cm OR ALC ≥ 25 x10^9/L AND any LN ≥ 5 cm.	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).
MRD Cohort: Pharmacokinetics (PK) of Ibrutinib When Dosed in Combination With Venetoclax: Observed Maximum Concentration (Cmax)		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)
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)		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)
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)		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)
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Terminal Elimination Rate Constant (λz)		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)
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Apparent Total Clearance at Steady-State (CLss/F)		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)
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Cmax		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)
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Tmax		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)
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: AUC0-24h		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)
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: CLss/F		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)
MRD Cohort: CRR (CR/CRi Rate)	CR/CRi rate is defined as the percentage of participants achieving a best overall response of CR or CRi per 2008 IWCLL criteria (Halleck et al.) on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurred earlier. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.	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.)
MRD Cohort: Overall Response Rate (ORR)	ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PRL) evaluated in accordance with the 2008 IWCLL criteria (Halleck et al). Participants who did not have any postbaseline response assessment were considered as non-responders. This table is based on response assessments performed on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Kaplan-Meier estimate. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.	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.)
MRD Cohort: Duration of Response (DOR) at 42 Months Landmark Time	Duration of response was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2008 IWCLL response criteria (Halleck et al.) and defined as the interval between the date of initial documentation of a response including PR with lymphocytosis, until disease progression (PD) or death from any cause, whichever occurred first. As the median DOR was not reached as of 67.0 months study follow-up, the Kaplan-Meier estimate of DOR at 42 months landmark time was presented. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.	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.)
MRD Cohort: MRD-Negativity Rate	MRD negativity rate is defined as the percentage of participants achieving MRD negativity, which is defined as <1 CLL cell per 10,000 leukocytes (<1 x 10^-4) as assessed by flow cytometry of a peripheral blood (PB) or bone marrow (BM) aspirate sample per central laboratory on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.	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.)
MRD Cohort: Kaplan-Meier Estimate of Progression Free Survival (PFS) Rate at 48 Months Landmark Time	PFS was defined as time from the first dose date of study treatment until disease progression (PD) or death from any cause, whichever occurs first. Assessment of PD was conducted in accordance with the 2008 IWCLL criteria (Halleck et al). As the median PFS was not reached as of the overall median 67.0 months study follow-up, the Kaplan-Meier estimate of PFS rate at 48 months landmark time was presented. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.	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.)
MRD Cohort: Kaplan-Meier Estimate of Overall Survival (OS) Rate at 48 Months Landmark Time	OS is defined as the time from the first dose date of study treatment until date of death due to any cause. As the median OS was not reached as of the overall median 67.0 months study follow-up, the Kaplan-Meier estimate of OS rate at 48 months landmark time was presented. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD: Randomized to Ibrutinib=69.1 months; Confirmed uMRD: Randomized to Placebo=67.4 months; uMRD Not Confirmed: Randomized to Open-Label Ibrutinib=47.9 months; uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax=47.9 months.	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.)
MRD Cohort: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs	An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires unplanned in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity of events were graded according to the Common Terminology Criteria for Adverse Events version 4.03: mild=grade1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5. Causal relation of study drug and event was assessed as not related, unlikely, possibly or probably related to the study drug.	From first dose until 30 days following last dose of study drug. Overall median treatment duration for the MRD cohort was 45.1 months.
FD Cohort: ORR	ORR is defined as the percentage of participants who achieve a best overall response CR, CRi, nPR, PR, or PRL as evaluated by investigator using 2008 IWCLL criteria (Halleck et al.). Participants who did not have any postbaseline response assessment were considered as non-responders. This table is based on response assessments performed on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Kaplan-Meier estimate.	From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months.
FD Cohort: DOR at 60 Months Landmark Time	Duration of response was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2008 IWCLL response criteria (Halleck et al.) and defined as the interval between the date of initial documentation of a response including PR with lymphocytosis, until disease progression (PD) or death from any cause, whichever occurred first. As the median DOR was not reached as of the median 27.9 months study follow-up, the Kaplan-Meier estimate of DOR at 60 months landmark time was presented.	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.
FD Cohort: MRD Negativity Rate	MRD negativity rate is defined as the percentage of participants achieving MRD negativity, which is defined as <1 CLL cell per 10,000 leukocytes (<1 x 10^-4) as assessed by flow cytometry of a peripheral blood (PB) or bone marrow (BM) aspirate sample per central laboratory on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier.	From randomization date until before any subsequent antineoplastic therapy, for a median follow-up of 69.0 months.
FD Cohort: Kaplan-Meier Estimate of PFS Rate at 66 Months Landmark Time	PFS was defined as time from the first dose date of study treatment until disease progression (PD) or death from any cause, whichever occurs first. Assessment of PD was conducted in accordance with the 2008 IWCLL criteria (Halleck et al). As the median PFS was not reached as of the median 69.0 months study follow-up, the Kaplan-Meier estimate of PFS rate at 66 months landmark time was presented.	From the first dose of ibrutinib to the first confirmed PD or death, for an median follow-up of 69.0 months.
FD Cohort: Kaplan-Meier Estimate of OS Rate at 66 Months Landmark Time	OS is defined as the time from the first dose date of study treatment until date of death due to any cause. As the median OS was not reached as of the median 69.0 months study follow-up, the Kaplan-Meier estimate of OS rate at 66 months landmark time was presented.	From the first dose of ibrutinib to time of death, for a median follow-up of 69.0 months.
FD Cohort: Percentage of Participants With TEAEs, Treatment-Emergent SAEs, and Discontinuations Due to TEAEs	An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires unplanned in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity of events were graded according to the Common Terminology Criteria for Adverse Events version 4.03: mild=grade1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5. Causal relation of study drug and event was assessed as not related, unlikely, possibly or probably related to the study drug.	From first dose until 30 days following last dose of study drug. Overall median treatment duration for the FD cohort was 13.8 months.

Collaborators and Investigators

• Sponsor: Pharmacyclics LLC.
• Collaborators: Janssen Research & Development, LLC
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

General Publications

• Wierda WG, Allan JN, Siddiqi T, Kipps TJ, Opat S, Tedeschi A, Badoux XC, Kuss BJ, Jackson S, Moreno C, Jacobs R, Pagel JM, Flinn I, Pak Y, Zhou C, Szafer-Glusman E, Ninomoto J, Dean JP, James DF, Ghia P, Tam CS. Ibrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results From the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE Study. J Clin Oncol. 2021 Dec 1;39(34):3853-3865. doi: 10.1200/JCO.21.00807. Epub 2021 Oct 7.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2016
• Primary Completion (Actual): November 12, 2020
• Study Completion (Actual): March 27, 2024

Study Registration Dates

• First Submitted: September 20, 2016
• First Submitted That Met QC Criteria: September 20, 2016
• First Posted (Estimated): September 22, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Venetoclax; Ibrutinib
• Other Study ID Numbers: PCYC-1142-CA; 2016-002293-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No