LeukemiaPhase 2CaptivateNCT02910583
Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)
A Phase 2 study testing ibrutinib and venetoclax in people with Leukemia and Chronic Lymphocytic Leukemia, run by Pharmacyclics LLC. at 46 sites in 6 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- ibrutinib and venetoclax
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 323 participants
- Where
- 46 sitesin 6 countries
- Study dates
- 28 Sep 2016to 27 Mar 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
46 sites in 6 countries.
46 sites in 6 countries
United States14 sites
Charlotte-Mecklenberg Hospital, Carolinas Healthcare System, Levine Cancer Inst /ID# 1142-0733
Charlotte, North Carolina, 28203
Tennessee Oncology - Chattanooga /ID# 1142-0123
Chattanooga, Tennessee, 37404-1108
Cleveland Clinic Foundation /ID# 1142-0739
Cleveland, Ohio, 44195
City of Hope /ID# 1142-0047
Duarte, California, 91010
MD Anderson Cancer Center /ID# 1142-0032
Houston, Texas, 77030
Moores Cancer Center at UC San Diego /ID# 1142-0241
La Jolla, California, 92093
Norton Cancer Center /ID# 1142-0071
Louisville, Kentucky, 40202
Rutgers Cancer Institute of New Jersey /ID# 1142-1193
New Brunswick, New Jersey, 08901
Northwell Health/Long Island Jewish Hospital /ID# 1142-0350
New Hyde Park, New York, 11042
New York Presbyterian Hospital/Weill Cornell Med College /ID# 1142-0200
New York, New York, 10021
UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1142-0008
Orange, California, 92868-3201
University of Pennsylvania /ID# 1142-0069
Philadelphia, Pennsylvania, 19104
University of Rochester Cancer Center /ID# 1142-0127
Rochester, New York, 14642-0001
Swedish Cancer Institute /ID# 1142-0114
Seattle, Washington, 98104
Spain9 sites
Hospital Clinic de Barcelona /ID# 1142-0533
Barcelona, 08036
Hospital Santa Creu i Sant Pau /ID# 1142-0535
Barcelona, 08041
Hospital Universitario Virgen de las Nieves /ID# 1142-1196
Granada, 18014
Hospital Duran i Reynals /ID# 1142-0604
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital Universitario Ramon y Cajal /ID# 1142-0874
Madrid, 28034
Hospital Universitario 12 de Octubre /ID# 1142-0864
Madrid, 28041
Hospital Universitario Puerta de Hierro, Majadahonda /ID# 1142-0536
Majadahonda, Madrid, 28222
Complejo Hospitalario de Navarra /ID# 1142-1197
Pamplona, Navarre, 31008
Hospital Clinico Universitario de Salamanca /ID# 1142-0790
Salamanca, 37007
Australia7 sites
Flinders Medical Centre /ID# 1142-0163
Bedford Park, South Australia, 5042
Monash Medical Centre /ID# 1142-0556
Clayton, Victoria, 3168
Peter MacCallum Cancer Centre-East Melbourne /ID# 1142-0633
East Melbourne, Victoria, 3002
St Vincent's Hospital Melbourne /ID# 1142-0501
Fitzroy, Victoria, 3065
Frankston Hospital /ID# 1142-0715
Frankston, Victoria, 3199
Austin Health /ID# 1142-0170
Heidelberg, Victoria, 3084
St George Hospital /ID# 1142-0654
Kogarah, New South Wales, 2217
Italy7 sites
Ospedale Policlinico San Martino /ID# 1142-0903
Genova, 16132
Ospedale San Raffaele IRCCS /ID# 1142-0523
Milan, Lombardy, 20132
ASST Grande Ospedale Metropolitano Niguarda /ID# 1142-0581
Milan, 20162
Azienda Ospedaliero-Universitaria di Modena /ID# 1142-0524
Modena, 41124
Azienda Ospedaliero Universitaria Maggiore della Carita di Novara /ID# 1142-0582
Novara, 28100
Azienda Ospedaliera di Padova /ID# 1142-1175
Padova, 35128
Azienda USL di Piacenza - Ospedale Guglielmo da Saliceto /ID# 1142-1182
Piacenza, 29121
Poland5 sites
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. /ID# 1142-0592
Brzozów, Podkarpackie Voivodeship, 36-200
Samodzielny Publiczny Szpital Klinczny Nr-1- Akademickie Cenrum Klinic /ID# 1142-0529
Gdansk, Pomeranian Voivodeship, 80-952
Malopolskie Centrum Medyczne /ID# 1142-0364
Krakow, Lesser Poland Voivodeship, 30-510
Medical Univ. of Lodz and Copernicus Memorial Hospital /ID# 1142-0531
Lodz, 93-510
Duplicate_Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie /ID# 1142-0590
Lublin, Lublin Voivodeship, 20-081
New Zealand4 sites
North Shore Hospital /ID# 1142-0663
Auckland, 0622
Christchurch Hospital /ID# 1142-0589
Christchurch, Canterbury, 8011
Middlemore Hospital /ID# 1142-0662
Otahuhu, Auckland, 2025
Palmerston North Hospital /ID# 1142-0585
Palmerston North, Manawatu-Wanganui, 4414
About this study
Official title: 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.
- Being tested
- ibrutinib, venetoclax, Placebo
- Medical subject headings
- Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ibrutinibDrug
ibrutinib administered orally once daily (three 140 mg capsules)
venetoclaxDrug
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.
PlaceboDrug
placebo capsules to match ibrutinib administered orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax | Experimental | 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. Receives: Drug: ibrutinib; Drug: venetoclax |
| MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded) | Experimental | 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. Receives: Drug: ibrutinib; Drug: venetoclax |
| MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded) | Placebo comparator | 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. Receives: Drug: ibrutinib; Drug: venetoclax; Drug: Placebo |
| MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label) | Experimental | 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. Receives: Drug: ibrutinib; Drug: venetoclax |
| MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label) | Experimental | 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. Receives: Drug: ibrutinib; Drug: venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months.
Secondary outcomes (24)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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: 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.
Measured: 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: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From the first dose of ibrutinib to time of death, for a median follow-up of 69.0 months.
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.
Measured: 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: 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.
Measured: From first dose until 30 days following last dose of study drug. Overall median treatment duration for the FD cohort was 13.8 months.
MRD Cohort: Pharmacokinetics (PK) of Ibrutinib When Dosed in Combination With Venetoclax: Observed Maximum Concentration (Cmax)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2016 (estimated)
- Study start28 Sep 2016
- Primary completion12 Nov 2020
- Study completion27 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 323 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmacyclics LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen Research & Development, LLC
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02910583
- Sponsor's protocol ID
- PCYC-1142-CA
- Other IDs
- 2016-002293-12, 2016
- Acronym
- Captivate
- Status last verified
- Nov 2024
- First submitted
- 20 Sep 2016
- Last updated
- 10 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
Publications
Castonguay M, Anderson MA, Thompson P, Seymour JF. Venetoclax retreatment in chronic lymphocytic leukemia is biologically rational and clinically effective. Blood Adv. 2026 May 26;10(10):3357-3366. doi: 10.1182/bloodadvances.2026019871.
PubMed 41843779Moreno C, Solman IG, Tam CS, Grigg A, Scarfo L, Kipps TJ, Srinivasan S, Mali RS, Zhou C, Dean JP, Szafer-Glusman E, Choi M. Immune restoration with ibrutinib plus venetoclax in first-line chronic lymphocytic leukemia: the phase 2 CAPTIVATE study. Blood Adv. 2023 Sep 26;7(18):5294-5303. doi: 10.1182/bloodadvances.2023010236.
PubMed 37315225Wierda 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.
PubMed 34618601