Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05650723 | Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based Obinutuzumab | PHASE2 | ACTIVE NOT_RECRUITING | 50 | — | — | May 8, 2023 | Dec 1, 2027 | Feb 25, 2026 | 1 | United States |
The primary endpoint of C16 peripheral blood MRD negativity at cycle 16 will be represented as a percentage of total patients. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution. A cycle is defined as 28 days.
The primary endpoint of C16 bone marrow MRD negativity at cycle 16 will be represented as a percentage of total patients. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution.
The co-primary endpoint of C23 peripheral blood MRD negativity rate will be presented as a percentage of patients that achieve undetectable MRD at C23, who were found to be MRD positive at C16 and went on to receive at least one dose of obinutuzumab. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution.
The co-primary endpoint of C23 bone marrow MRD negativity rate will be presented as a percentage of patients that achieve undetectable MRD at C23, who were found to be MRD positive at C16 and went on to receive at least one dose of obinutuzumab. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution.
| Arm | Type | Description |
|---|---|---|
| Double Therapy (Zanubrutinib plus Venetoclax) | EXPERIMENTAL | All participants will receive an initial 3 cycles of zanubrutinib monotherapy. This lead-in period will then be followed by 12 cycles of zanubrutinib and venetoclax combination therapy. All participants will complete 12 cycles of zanubrutinib and venetoclax combination therapy or 15 cycles of total treatment. Peripheral blood and bone marrow MRD assessments will occur at C16D1. Participants will continue on double combination treatment for an additional 1 month while results of MRD testing are obtained. In total, all participants will be on treatment for at least 16 full cycles. Participants that meet definition of MRD negativity will stop therapy at C17D1 and enter an observation phase with study visits every 3 months. Participants that remain MRD positive at C16D1 will enter the triple therapy (zanubrutinib, venetoclax, and obinutuzumab) arm. |
| Triple Therapy (Zanubrutinib, Venetoclax, and Obinutuzumab) | EXPERIMENTAL | Participants that meet definition of MRD positivity at C16D1 will enter the triple therapy arm (zanubrutinib, venetoclax, and obinutuzumab). These participants will continue combination therapy with zanubrutinib and venetoclax, but will also receive 6 cycles of obinutuzumab starting at C17D1. In this subgroup, peripheral blood and bone marrow MRD assessments will occur after an additional 6 cycles of the triplet combination therapy (C23D1) at which point all participants will stop study treatment regardless of MRD status. |
| Name | Type | Description |
|---|---|---|
| Zanubrutinib Pill | DRUG | 320 mg once per day by mouth |
| Venetoclax Pill | DRUG | 400 mg once per day by mouth following the standard ramp-up schedule (20mg daily PO week 1, 50mg daily PO week 2, 100mg daily PO week 3, 200mg daily PO week 4, followed by 400mg PO daily week 5) |
| Obinutuzumab Injection | DRUG | 1000 mg IV given every 28 days |
Inclusion Criteria 1. Subject must be able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures. 2. Subject must be ≥ 18 years of age. 3. Subject mu...