Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial
Phase 3NCT00112931
- Population
- Asymptomatic adults with advanced-stage, low-tumour-burden follicular lymphoma (grades 1, 2 and 3a).
- Design
- Open-label randomised phase 3 trial in 118 centres (UK, Australia, New Zealand, Turkey and Poland) of asymptomatic adults with low-tumour-burden follicular lymphoma (grades 1, 2 and 3a), allocated 1:1:1 to watchful waiting, rituximab induction (375 mg/m2 weekly for 4 weeks) or rituximab induction followed by 12 further infusions at 2-monthly intervals for 2 years (maintenance rituximab). Recruitment to the induction group closed on 30 September 2007 and the study became two-arm. 379 patients were randomised to watchful waiting or maintenance rituximab and 84 to induction.
- Primary endpoint
- Time to new treatment, Quality of life at month 7
- Arms
- Watchful waiting (control): Watchful waiting until treatment was needed
- Rituximab induction (experimental, n = 84): Rituximab 375 mg/m2 weekly for 4 weeks
- Rituximab maintenance (experimental): Rituximab induction followed by 12 further infusions at 2-monthly intervals for 2 years
- People
- Ardeshna KM
Time to new treatmentHR 0.21 (95% CI 0.14–0.31)Δ 36-month Time to new treatment+42 pointsTime to new treatmentHR 0.35 (95% CI 0.22–0.56)
Show the numbers
| Endpoint | Analysis | Rituximab induction / Rituximab maintenance | Watchful waiting | Effect |
|---|---|---|---|---|
| Time to new treatmentAll randomly assigned patients (intention to treat)Time to start of new treatment (chemotherapy or radiotherapy). | primaryArdeshna 2014 | 88% at 3 y (83–92%) | 46% at 3 y (39–53%) | HR 0.21 (95% CI 0.14–0.31)P<0.0001Proportion not needing new treatment at 3 years. Comparison of maintenance rituximab with watchful waiting. |
| Time to new treatmentAll randomly assigned patients (intention to treat)Time to start of new treatment (chemotherapy or radiotherapy). | primaryArdeshna 2014 | 78% at 3 y (69–87%) | — | HR 0.35 (95% CI 0.22–0.56)P<0.0001Proportion not needing new treatment at 3 years with rituximab induction; hazard ratio is versus watchful waiting. The abstract gives a hazard ratio of 0.75 (95% CI 0.41 to 1.34; p=0.33) for induction versus maintenance rituximab. |
| Endpoint | Analysis | Rituximab induction / Rituximab maintenance | Watchful waiting | Effect |
|---|---|---|---|---|
| Time to new treatmentAll randomly assigned patients (intention to treat)Time to start of new treatment (chemotherapy or radiotherapy). | primaryArdeshna 2014 | 88% at 3 y (83–92%) | 46% at 3 y (39–53%) | HR 0.21 (95% CI 0.14–0.31)P<0.0001Proportion not needing new treatment at 3 years. Comparison of maintenance rituximab with watchful waiting. |
| Time to new treatmentAll randomly assigned patients (intention to treat)Time to start of new treatment (chemotherapy or radiotherapy). | primaryArdeshna 2014 | 78% at 3 y (69–87%) | — | HR 0.35 (95% CI 0.22–0.56)P<0.0001Proportion not needing new treatment at 3 years with rituximab induction; hazard ratio is versus watchful waiting. The abstract gives a hazard ratio of 0.75 (95% CI 0.41 to 1.34; p=0.33) for induction versus maintenance rituximab. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| Time to new treatment | 0.21 | 0.14–0.31 |
| Time to new treatment | 0.35 | 0.22–0.56 |