Phase 2
N=323
Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)
Leukemia · Chronic Lymphocytic Leukemia · Small Lymphocytic Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT02910583 ↗Enrolled (actual)
323
Serious AEs
19.7%
Results posted
Feb 2022
Primary outcome: Primary: MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants — 100.0; 95.3 percentage of participants — p=0.1475
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ibrutinib (Drug); venetoclax (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pharmacyclics LLC.
- Primary completion
- Nov 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants |
100.0; 95.3 | 0.1475 |
| PRIMARY FD Cohort: Complete Response Rate (CRR; Complete Response/Complete Response With Incomplete Blood Count Recovery [CR/CRi]) Rate |
58.1; 57.2 | < 0.0001 sig |
| SECONDARY MRD Cohort: CRR (CR/CRi Rate) |
66.5; 79.1; 65.1; 77.4; 56.3 | — |
| SECONDARY MRD Cohort: Overall Response Rate (ORR) |
97.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY MRD Cohort: Duration of Response (DOR) at 42 Months Landmark Time |
93.5; 97.6; 93.0; 96.7; 93.2 | — |
| SECONDARY MRD Cohort: MRD-Negativity Rate |
81.7; 65.1; 51.6; 78.1; 77.4; 55.6 | — |
| SECONDARY 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) |
90.0 | — |
| SECONDARY MRD Cohort: Kaplan-Meier Estimate of Progression Free Survival (PFS) Rate at 48 Months Landmark Time |
90.9; 97.6; 88.2; 93.3; 93.2 | — |
| SECONDARY MRD Cohort: Kaplan-Meier Estimate of Overall Survival (OS) Rate at 48 Months Landmark Time |
98.0; 97.6; 100.0; 96.7; 100.0 | — |
| SECONDARY MRD Cohort: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs |
100.0; 100.0; 100.0; 100.0; 100.0; 75.6 | — |
| SECONDARY FD Cohort: ORR |
95.6; 96.2 | — |
| SECONDARY FD Cohort: DOR at 60 Months Landmark Time |
63.6; 60.5 | — |
| SECONDARY FD Cohort: MRD Negativity Rate |
78.7; 78.6; 61.8; 59.7; 76.5; 76.7 | — |
| SECONDARY FD Cohort: Kaplan-Meier Estimate of PFS Rate at 66 Months Landmark Time |
63.2; 60.2 | — |
| SECONDARY FD Cohort: Kaplan-Meier Estimate of OS Rate at 66 Months Landmark Time |
96.9; 96.1 | — |
| SECONDARY FD Cohort: TLS Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in) |
94.1 | — |
| SECONDARY FD Cohort: Percentage of Participants With TEAEs, Treatment-Emergent SAEs, and Discontinuations Due to TEAEs |
99.4; 62.3; 92.5; 44.7; 84.3; 45.3 | — |
| SECONDARY MRD Cohort: Pharmacokinetics (PK) of Ibrutinib When Dosed in Combination With Venetoclax: Observed Maximum Concentration (Cmax) |
88.5 | — |
| SECONDARY 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) |
2.00; 24.0; 5.30 | — |
| SECONDARY 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) |
504; 480 | — |
| SECONDARY MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Terminal Elimination Rate Constant (λz) |
0.132 | — |
| SECONDARY MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Apparent Total Clearance at Steady-State (CLss/F) |
833 | — |
| SECONDARY MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Cmax |
3034 | — |
| SECONDARY MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Tmax |
6.00 | — |
| SECONDARY MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: AUC0-24h |
48993 | — |
| SECONDARY MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: CLss/F |
8.16 | — |
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.
Eligibility Criteria
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)
Data sourced from ClinicalTrials.gov (NCT02910583). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.