Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)
- Conditions
- LeukemiaChronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma
- Interventions
- Registration Number
- NCT02910583
- Lead Sponsor
- Pharmacyclics LLC.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 323
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded) Placebo 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. Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax ibrutinib 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. Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax 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. MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded) ibrutinib 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. MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded) venetoclax 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. MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded) ibrutinib 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. MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded) venetoclax 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. MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label) ibrutinib 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. MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label) venetoclax 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. MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label) ibrutinib 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. MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label) venetoclax 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.
- Primary Outcome Measures
Name Time Method MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants 1 year after randomization 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.
FD Cohort: Complete Response Rate (CRR; Complete Response/Complete Response With Incomplete Blood Count Recovery [CR/CRi]) Rate From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months. 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.
- Secondary Outcome Measures
Name Time Method 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: CRR (CR/CRi Rate) 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.) 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.MRD Cohort: Overall Response Rate (ORR) 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.) 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.MRD Cohort: Duration of Response (DOR) at 42 Months Landmark Time 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.) 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.MRD Cohort: MRD-Negativity Rate 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 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.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) 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). 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.
MRD Cohort: Kaplan-Meier Estimate of Progression Free Survival (PFS) Rate at 48 Months Landmark Time 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.) 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.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: Kaplan-Meier Estimate of Overall Survival (OS) Rate at 48 Months Landmark Time 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.) 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.MRD Cohort: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs From first dose until 30 days following last dose of study drug. Overall median treatment duration for the MRD cohort was 45.1 months. 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.
FD Cohort: ORR From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months. 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.
FD Cohort: DOR at 60 Months Landmark Time 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. 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.
FD Cohort: MRD Negativity Rate From randomization date until before any subsequent antineoplastic therapy, for a median follow-up of 69.0 months. 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.
FD Cohort: Kaplan-Meier Estimate of PFS Rate at 66 Months Landmark Time From the first dose of ibrutinib to the first confirmed PD or death, for an median follow-up of 69.0 months. 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.
FD Cohort: Kaplan-Meier Estimate of OS Rate at 66 Months Landmark Time From the first dose of ibrutinib to time of death, for a median follow-up of 69.0 months. 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.
FD Cohort: TLS Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in) 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). 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.
FD Cohort: Percentage of Participants With TEAEs, Treatment-Emergent SAEs, and Discontinuations Due to TEAEs From first dose until 30 days following last dose of study drug. Overall median treatment duration for the FD cohort was 13.8 months. 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.
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)
Trial Locations
- Locations (46)
University of Pennsylvania /ID# 1142-0069
🇺🇸Philadelphia, Pennsylvania, United States
St Vincent's Hospital Melbourne /ID# 1142-0501
🇦🇺Fitzroy, Victoria, Australia
Tennessee Oncology - Chattanooga /ID# 1142-0123
🇺🇸Chattanooga, Tennessee, United States
Cleveland Clinic Foundation /ID# 1142-0739
🇺🇸Cleveland, Ohio, United States
MD Anderson Cancer Center /ID# 1142-0032
🇺🇸Houston, Texas, United States
Swedish Cancer Institute /ID# 1142-0114
🇺🇸Seattle, Washington, United States
UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1142-0008
🇺🇸Orange, California, United States
City of Hope /ID# 1142-0047
🇺🇸Duarte, California, United States
Moores Cancer Center at UC San Diego /ID# 1142-0241
🇺🇸La Jolla, California, United States
Northwell Health/Long Island Jewish Hospital /ID# 1142-0350
🇺🇸New Hyde Park, New York, United States
Norton Cancer Center /ID# 1142-0071
🇺🇸Louisville, Kentucky, United States
Rutgers Cancer Institute of New Jersey /ID# 1142-1193
🇺🇸New Brunswick, New Jersey, United States
New York Presbyterian Hospital/Weill Cornell Med College /ID# 1142-0200
🇺🇸New York, New York, United States
University of Rochester Cancer Center /ID# 1142-0127
🇺🇸Rochester, New York, United States
Charlotte-Mecklenberg Hospital, Carolinas Healthcare System, Levine Cancer Inst /ID# 1142-0733
🇺🇸Charlotte, North Carolina, United States
Monash Medical Centre /ID# 1142-0556
🇦🇺Clayton, Victoria, Australia
Flinders Medical Centre /ID# 1142-0163
🇦🇺Bedford Park, South Australia, Australia
Peter MacCallum Cancer Centre-East Melbourne /ID# 1142-0633
🇦🇺East Melbourne, Victoria, Australia
St George Hospital /ID# 1142-0654
🇦🇺Kogarah, New South Wales, Australia
Austin Health /ID# 1142-0170
🇦🇺Heidelberg, Victoria, Australia
Frankston Hospital /ID# 1142-0715
🇦🇺Frankston, Victoria, Australia
Ospedale San Raffaele IRCCS /ID# 1142-0523
🇮🇹Milan, Lombardia, Italy
Ospedale Policlinico San Martino /ID# 1142-0903
🇮🇹Genova, Italy
ASST Grande Ospedale Metropolitano Niguarda /ID# 1142-0581
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria Maggiore della Carita di Novara /ID# 1142-0582
🇮🇹Novara, Italy
Azienda Ospedaliero-Universitaria di Modena /ID# 1142-0524
🇮🇹Modena, Italy
Azienda Ospedaliera di Padova /ID# 1142-1175
🇮🇹Padova, Italy
Azienda USL di Piacenza - Ospedale Guglielmo da Saliceto /ID# 1142-1182
🇮🇹Piacenza, Italy
Christchurch Hospital /ID# 1142-0589
🇳🇿Christchurch, Canterbury, New Zealand
Middlemore Hospital /ID# 1142-0662
🇳🇿Otahuhu, Auckland, New Zealand
Palmerston North Hospital /ID# 1142-0585
🇳🇿Palmerston North, Manawatu-Wanganui, New Zealand
Duplicate_Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie /ID# 1142-0590
🇵🇱Lublin, Lubelskie, Poland
Malopolskie Centrum Medyczne /ID# 1142-0364
🇵🇱Krakow, Malopolskie, Poland
North Shore Hospital /ID# 1142-0663
🇳🇿Auckland, New Zealand
Samodzielny Publiczny Szpital Klinczny Nr-1- Akademickie Cenrum Klinic /ID# 1142-0529
🇵🇱Gdańsk, Pomorskie, Poland
Medical Univ. of Lodz and Copernicus Memorial Hospital /ID# 1142-0531
🇵🇱Lodz, Poland
Hospital Duran i Reynals /ID# 1142-0604
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Puerta de Hierro, Majadahonda /ID# 1142-0536
🇪🇸Majadahonda, Madrid, Spain
Hospital Universitario Virgen de las Nieves /ID# 1142-1196
🇪🇸Granada, Spain
Hospital Universitario Ramon y Cajal /ID# 1142-0874
🇪🇸Madrid, Spain
Hospital Santa Creu i Sant Pau /ID# 1142-0535
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona /ID# 1142-0533
🇪🇸Barcelona, Spain
Hospital Clinico Universitario de Salamanca /ID# 1142-0790
🇪🇸Salamanca, Spain
Hospital Universitario 12 de Octubre /ID# 1142-0864
🇪🇸Madrid, Spain
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. /ID# 1142-0592
🇵🇱Brzozow, Podkarpackie, Poland
Complejo Hospitalario de Navarra /ID# 1142-1197
🇪🇸Pamplona, Navarra, Spain