Comparison of High-Dose Chemotherapy + Rituximab and CHOP + Rituximab in High-Risk Follicular Lymphoma

Phase 3

• Conditions: Follicular Lymphoma

• Registration Number: NCT00435955
• Lead Sponsor: Azienda Ospedaliera San Giovanni Battista

Brief Summary

The purpose of this study is to determine whether an intensified treatment plus Rituximab followed by autologous transplantation is superior to a conventional chemotherapy regimen also supplemented with Rituximab.

Detailed Description

The place of intensified regimens with autologous stem cell transplantation (ASCT) is poorly defined in FL at diagnosis . Most data arise from studies performed in the pre-Rituximab age. According to these studies, ASCT improved overall survival versus standard salvage approaches in relapsed patients with a high proportion of patients achieving a durable molecular remission. Data at diagnosis are less clear. Three studies have been so far published with contradictory results. Two of these studies showed that intensive therapy ensures a better disease control although in one study a significant extra-mortality from secondary tumors was observed in the intensified arm. A third study found no advantage for patients treated intensively. These results led to the widespread notion that ASCT is not superior to conventional chemotherapy in unselected FL patients. Our previous non-randomized experience employing high dose sequential chemotherapy with a final TBI-free ASCT added some clues to these considerations. Our study employs an autografting procedure which is associated to fewer secondary tumors as it does not include total body irradiation. Moreover we have observed that the our regimen (named HDS) is particularly effective in high-risk patients, suggesting that this specific subgroup is the most appropriate setting for intensified regimens

The present multicenter open label randomized trial took advantage of these observations. In addition we have included Rituximab in both arms as the inclusion of this novel agent is expected to significantly modify the performance of available treatments. We have thus compared a Rituximab-supplemented version of HDS (R-HDS) regimen with six CHOP courses supplemented by an identical number of Rituximab courses. Aim of the study was verify if an intensified approach could be beneficial as first line treatment of high-risk FL patients in the Rituximab age.

Study Timeline

• Study Start: 2000-03
• Status Verified: 2007-02
• Study First Submitted: 2007-02-15
• Study First Submitted QC: 2007-02-15
• Last Update Submitted: 2007-02-15
• Study First Posted: 2007-02-16
• Last Update Posted: 2007-02-16

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1. Follicular Lymphoma at diagnosis
2. Stage >I
3. age-adjusted I.P.I. score 2 or 3 or three or more adverse factors of the I.L.I. score

Exclusion Criteria

1. Serum positivity for HIV, HCV. HBsAg-positive only if active viral replication, assessed by HBV-DNA was present.
2. Major alterations of heart, lung, kidneys, liver, except for those directly disease-related;
3. Evidence of second tumors;
4. Previous chemotherapy( except patients who received limited radiotherapy);
5. Cerebral or CNS involvement.
6. Drug addiction or severe psychiatric disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Event free survival at three years

Secondary Outcome Measures

Name	Time	Method
Overall survival
CR rate
Progression free survival
Disease free survival I
Incidence of secondary myelodisplasia and solid cancer
Rate of molecular remission
Predictive value of molecular remission

Trial Locations

Locations (1)

Divisione di Ematologia Universitaria; 🇮🇹 Torino, Italy