NCT00137995

R-ICE Versus R-DHAP in Patients Aged 18-65 With Relapse Diffuse Large B-cell Lymphoma

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 481 (actual)
• Sponsor: Lymphoma Study Association · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this study is to evaluate the efficacy and safety of induction therapy R-ICE in comparison to R-DHAP after 3 cycles adjusted to successful mobilization of stem cells in patients with previously treated diffuse large B-cell lymphoma CD20. The goal is to detect a difference in mobilization adjusted response rate of 15% between R-ICE and R-DHAP. The other objective is to evaluate the efficacy and safety of MabThera maintenance therapy after transplantation as measured by the event free survival. The goal is to obtain a 15% increase of event free survival at 2 years.

Detailed description

In vitro, the addition of rituximab to standard anticancer drugs increases cell lyses even in chemoresistant cell lines. This chemosensitization effect was also demonstrated in vivo by the results of the GELA trial in elderly patients with DLCL. Reported phase II study results on the RICE regimen for treatment of patients with relapsed DLCL and comparison with historical controls being treated with ICE suggests that this effect (15% improvement in response rate) is likely in relapsing DLCL and had led the SWOG to stop a randomized trial comparing ICE vs RICE in patients with relapsed aggressive lymphoma. In the setting of relapsed DLCL, high dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard to improve survival in highly selected chemosensitive patients. In the Parma study, only 58% of the patients with relapsed aggressive NHL were good responders after DHAP and 24% were in complete remission. Moreover, the quality of response depended on prognostic factors such as IPI and relapse \> 12 months after treatment, and only patients responding to salvage therapy benefited from HDT + ASCT. As shown in the PARMA study. The goal in relapsed DLCL is to improve complete response rates before transplantation as it is the main parameter for eligibility for HDT + ASCT and the main prognostic factor. Unlike first line treatment with CHOP, no standard chemotherapy exists for relapsing patients. DHAP has been the most frequently used regimen for decades but incorporates only two drugs, and has dose-limiting renal toxicity. The ICE regimen was developed at several dosages and studies consistently produced CR rates that were 10-15% superior to DHAP. It is expected that this difference will remain the same with the addition of rituximab to both regimens. Recent phase II data in patients with relapsed DLCL not previously treated with rituximab showed that RICE produced a response rate of 78% with a complete remission rate of 58% and was active in primary refractory disease as well as in intermediate-high risk patients (IPI 2-3). Association of DHAP to Rituximab, R-DHAP has been done on small series of patients by investigators, including patients relapsing after autotransplant. Despite numerous phase II studies, no randomized study has been performed comparing the two regimens (DHAP/ICE) or others in relapsing DLCL. Treatment of first line DLCL has been changed in the past 10 years with more intensive regimens, often followed by ASCT, and very recently with the addition of rituximab to chemotherapy and therefore the population of relapsing patients might be different from the one in the initial PARMA study. A large lymphoma intergroup study working on a large prospective data base might help to find the best salvage regimen and to assess the role of retreatment with monoclonal antibodies in these patients. Finally, the role of rituximab maintenance therapy after HDT + ASCT in prolonging second complete response should be evaluated.

Conditions

• Lymphoma, Large-Cell, Diffuse

Interventions

Type	Name	Description
DRUG	Rituximab	375 mg/m² D-2/D1
DRUG	Etoposide	100 mg/m² D1-D2-D3
DRUG	Carboplatine	max 800mg D2
DRUG	Ifosfamide + Mesna	5 g/m² from D2 to D13
DRUG	Cisplatine	100 mg/m² from D1 to D13
DRUG	Cytosine Arabinoside	2000 mg/m²/12 h D2 D3
DRUG	Dexamethasone	40 mg From D1 to D4
PROCEDURE	Autologous Stem Cell Transplantation
DRUG	BCNU	300mg/m² on D-6
DRUG	Etoposide	200 mg/m² from D-6 to D-3
DRUG	Cytarabine	100 mg/m² from D-6 to D-3
DRUG	Melphalan	140 mg/m² on D-2

Timeline

• Start date: 2003-06-01
• Primary completion: 2008-10-01
• Completion: 2008-10-01
• First posted: 2005-08-30
• Last updated: 2019-08-28

Locations

10 sites across 10 countries: United States, Australia, Belgium, Czechia, Finland, Germany, Israel, Sweden, Switzerland, United Kingdom

Regulatory

• FDA-regulated drug study