CORAL
Randomized Study of ICE Plus RITUXIMAB Versus DHAP Plus Rituximab in Previously Treated Patients With Diffuse Large B-cell Lymphoma, Followed by Randomized Maintenance With Rituximab
Phase 3N = 396NCT00137995
- Population
- Patients with CD20-positive diffuse large B-cell lymphoma in first relapse or refractory after first-line therapy; median age 55 years.
- Design
- Randomised comparison of two salvage regimens before high-dose therapy and autologous stem-cell transplantation (ASCT): patients with CD20-positive diffuse large B-cell lymphoma in first relapse or refractory after first-line therapy were randomly assigned to R-ICE or R-DHAP; responders after three cycles received high-dose chemotherapy and ASCT. The 2010 report describes 396 patients randomly assigned (388 treated); its primary end point was the mobilisation-adjusted response rate after three cycles. The final 2012 report describes 477 patients randomly assigned to a salvage regimen, of whom 242 were randomly assigned after ASCT to rituximab maintenance every 2 months for 1 year or observation; the primary end point of that second randomisation was event-free survival. ClinicalTrials.gov lists 481 enrolled.
- Primary endpoint
- Response rate, EFS
- Arms
- R-DHAP (control, n = 194): Rituximab, dexamethasone, high-dose cytarabine and cisplatin, then high-dose chemotherapy and ASCT in responders
- R-ICE (experimental, n = 202): Rituximab, ifosfamide, etoposide and carboplatin, then high-dose chemotherapy and ASCT in responders
- Observation after ASCT (control, n = 120): Observation only after autologous stem-cell transplantation
- Rituximab maintenance after ASCT (experimental, n = 122): Rituximab every 2 months for 1 year after autologous stem-cell transplantation
- People
- Gisselbrecht C, senior author Schmitz N, Intergroup study sponsored by GELA Recherche Clinique (GELARC)
Δ Response rate+0.7 pointsΔ Response rate−2.2 pointsΔ 36-month EFS−9 pointsΔ 48-month EFS−1 points
Show the numbers
| Endpoint | Analysis | R-ICE / Rituximab maintenance after ASCT | R-DHAP / Observation after ASCT | Effect |
|---|---|---|---|---|
| Response ratePatients who received at least one injection of study treatment (388: 197 with R-ICE, 191 with R-DHAP; Table 2 of the full text); 396 were randomly assignedResponse rate after three cycles of salvage therapy, as reported; the abstract gives no further definition. | primaryGisselbrecht 2010 | 63.5% (56–70%) | 62.8% (55–69%) | Overall response (complete, unconfirmed complete or partial) after three cycles, a measure distinct from the primary end point (see the mobilisation-adjusted result). The abstract prints the R-DHAP interval as '95 CI, 55% to 69%'; the full text prints 56.8% to 70.7% and 55.6% to 69.7%. |
| Response ratePatients who received at least one injection of study treatment (388: 197 with R-ICE, 191 with R-DHAP); 396 were randomly assignedMobilisation-adjusted response rate after three cycles: objective response (complete, unconfirmed complete or partial) associated with the target stem-cell mobilisation of at least 2,000,000 CD34-positive cells per kg (stated primary end point of the induction phase). | primaryGisselbrecht 2010 | 52.3% | 54.5% | 103 of 197 patients with R-ICE and 104 of 191 with R-DHAP; collection failure (fewer than 2,000,000 CD34-positive cells per kg) occurred in 20 and 15 patients. No confidence interval or P value for this comparison was read. |
| EFSRandomised patients; the analysis population for this estimate is not stated in the sentence readEvent-free survival: time from the start of treatment to progression, relapse, new treatment or death from any cause. | primarymedian follow-up 27 monthsGisselbrecht 2010 | 26% at 3 y | 35% at 3 y | P=.6Both regimens combined: 3-year EFS 31% (95% CI 26 to 36). Three-year overall survival was 47% with R-ICE and 51% with R-DHAP (P=.4); 3-year progression-free survival 31% and 42% (P=.4). The abstract states only that there was no significant difference. |
| EFSPatients randomly assigned after ASCT to rituximab maintenance (122) or observation (120)Event-free survival after ASCT, rituximab maintenance versus observation (separate second randomisation). | finalmedian follow-up 44 monthsGisselbrecht 2012 | 52% at 4 y | 53% at 4 y | P=.7Rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with six deaths versus three in the observation arm. |
| Endpoint | Analysis | R-ICE / Rituximab maintenance after ASCT | R-DHAP / Observation after ASCT | Effect |
|---|---|---|---|---|
| Response ratePatients who received at least one injection of study treatment (388: 197 with R-ICE, 191 with R-DHAP; Table 2 of the full text); 396 were randomly assignedResponse rate after three cycles of salvage therapy, as reported; the abstract gives no further definition. | primaryGisselbrecht 2010 | 63.5% (56–70%) | 62.8% (55–69%) | Overall response (complete, unconfirmed complete or partial) after three cycles, a measure distinct from the primary end point (see the mobilisation-adjusted result). The abstract prints the R-DHAP interval as '95 CI, 55% to 69%'; the full text prints 56.8% to 70.7% and 55.6% to 69.7%. |
| Response ratePatients who received at least one injection of study treatment (388: 197 with R-ICE, 191 with R-DHAP); 396 were randomly assignedMobilisation-adjusted response rate after three cycles: objective response (complete, unconfirmed complete or partial) associated with the target stem-cell mobilisation of at least 2,000,000 CD34-positive cells per kg (stated primary end point of the induction phase). | primaryGisselbrecht 2010 | 52.3% | 54.5% | 103 of 197 patients with R-ICE and 104 of 191 with R-DHAP; collection failure (fewer than 2,000,000 CD34-positive cells per kg) occurred in 20 and 15 patients. No confidence interval or P value for this comparison was read. |
| EFSRandomised patients; the analysis population for this estimate is not stated in the sentence readEvent-free survival: time from the start of treatment to progression, relapse, new treatment or death from any cause. | primarymedian follow-up 27 monthsGisselbrecht 2010 | 26% at 3 y | 35% at 3 y | P=.6Both regimens combined: 3-year EFS 31% (95% CI 26 to 36). Three-year overall survival was 47% with R-ICE and 51% with R-DHAP (P=.4); 3-year progression-free survival 31% and 42% (P=.4). The abstract states only that there was no significant difference. |
| EFSPatients randomly assigned after ASCT to rituximab maintenance (122) or observation (120)Event-free survival after ASCT, rituximab maintenance versus observation (separate second randomisation). | finalmedian follow-up 44 monthsGisselbrecht 2012 | 52% at 4 y | 53% at 4 y | P=.7Rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with six deaths versus three in the observation arm. |
Appears in
Sources
Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184-90.
Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012;30(36):4462-9.