A newer report of this study has been published: Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study (2024)
Many people with CLL are older and have other illnesses such as kidney or heart problems. This study showed that a limited one-year course of treatment with venetoclax tablets and obinutuzumab injections controls the disease much better than an older treatment. An important advantage of this approach is that treatment stops after one year, so the patient does not have to take medicine for years.
Untreated CLL (in CLL14, patients with comorbidities)
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab | 100 mg Day 1, 900 mg Day 2, 1,000 mg Days 8 and 15 | IV | Days 1, 2, 8 and 15 |
| Cycles 2–6 | |||
| Obinutuzumab | 1,000 mg | IV | Day 1 |
| From Day 22 of Cycle 1 | |||
| Venetoclax | Weekly ramp-up: 20, 50, 100, 200, then 400 mg | Oral, with food | Through the end of Cycle 12 at 400 mg |
Premedication before obinutuzumab.
Untreated CLL (in CLL14, patients with comorbidities)
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab | 100 mg (Day 1), 900 mg (Day 2), 1000 mg (Days 8 and 15) | IV | Days 1, 2, 8 and 15 |
| Cycles 2–6 | |||
| Obinutuzumab | 1000 mg | IV | Day 1 |
| From Day 22 of cycle 1: 5-week ramp-up | |||
| Venetoclax | 20, 50, 100, 200 and then 400 mg (one step each week) | Oral, with food | Until Day 28 of cycle 2 |
| Cycles 3–12 | |||
| Venetoclax | 400 mg once daily | Oral, with food | Continuous |
Give premedication before each obinutuzumab infusion; boxed warning: hepatitis B reactivation (screening mandatory) and PML.
On the page “Leukaemia” · Regimens and dosing in CLL: fixed-duration targeted therapy
Previously untreated (or treated) CLL/SLL
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab | Day 1: 100 mg; day 2: 900 mg; days 8 and 15: 1000 mg | IV | Days 1, 2, 8 and 15 |
| Cycles 2 to 6 | |||
| Obinutuzumab | 1000 mg | IV | Day 1 |
| From day 22 of cycle 1 (ramp-up ends on day 28 of cycle 2) | |||
| Venetoclax | Week 1: 20; week 2: 50; week 3: 100; week 4: 200; from week 5: 400 mg | Oral, with food and water | Once a day |
| Cycles 3 to 12 | |||
| Venetoclax | 400 mg | Oral | Daily |
On the page “Venetoclax (Venclexta)” · Dose and schedule (FDA label)
Previously untreated CLL (especially with comorbidities or a preference for fixed-duration treatment)
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab | 100 mg on day 1 and 900 mg on day 2, then 1000 mg | IV | Days 1 and 2, 8 and 15 |
| Cycles 2 to 6 | |||
| Obinutuzumab | 1000 mg | IV | Day 1 |
| From day 22 of cycle 1 | |||
| Venetoclax (ramp-up) | 20, 50, 100, 200 and 400 mg, one week each | Oral, with food | Daily |
| Until the end of cycle 12 | |||
| Venetoclax | 400 mg | Oral | Daily |
As in CLL14.
Dose source:.
On the page “Venetoclax and obinutuzumab in CLL (the 12-month CLL14 regimen)”
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Obinutuzumab IV for 6 cycles of 28 days: cycle 1 day 1 (100 mg, and 900 mg on day 2 if the dose is split) or 1000 mg, then 1000 mg on days 8 and 15 of cycle 1, and 1000 mg on day 1 of cycles 2 to 6.
Venetoclax orally with gradual dose ramp-up from day 22 of cycle 1: 20 mg (cycle 1, days 22 to 28), 50, 100 and 200 mg each for one week in cycle 2, then 400 mg daily until the end of cycle 12.
Obinutuzumab on the same schedule for 6 cycles, with chlorambucil 0.5 mg per kg orally on days 1 and 15 of each 28-day cycle for 12 cycles.
Source of the regimen details: ClinicalTrials.gov NCT02242942 (dosing schedule of venetoclax, obinutuzumab and chlorambucil)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients with previously untreated chronic lymphocytic leukaemia (CLL) and coexisting conditions: a Cumulative Illness Rating Scale (CIRS) score greater than 6 or a calculated creatinine clearance below 70 mL per minute. Median age 72 years, median CIRS 8.
Primary endpoint: investigator-assessed progression-free survival.
Secondary endpoints: MRD negativity, response rate, overall survival and safety.
Grade 3 or 4 neutropenia: 52.8% versus 48.1%; grade 3 or 4 infection: 17.5% versus 15.0%; death from any cause: 9.3% versus 7.9% (differences not significant). Gradual venetoclax dose ramp-up and tumour lysis syndrome prophylaxis and monitoring are essential.
Based on this study, the FDA approved venetoclax with obinutuzumab in 2019 for first-line treatment of CLL, and the EMA also approved it. This fixed-duration (12-month) regimen, alongside BTK inhibitors (such as ibrutinib, acalabrutinib and zanubrutinib), has become one of the two standard first-line approaches in CLL; later long-term follow-up (5 and 6 years) has shown the benefit to be durable.
The comparator (chlorambucil-obinutuzumab) is no longer considered standard for most patients today, and there was no direct comparison with BTK inhibitors. The study was open-label and enrolled only patients with coexisting conditions. At the time of this report no overall survival benefit had been shown.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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