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

• ClinicalTrials.gov Identifier: NCT00435955
• Recruitment Status: Unknown
• First Posted: February 16, 2007
• Last Update Posted: February 16, 2007
• Sponsor: Azienda Ospedaliera San Giovanni Battista
• Collaborators: University of Turin, Italy; Gruppo Italiano Trapianto di Midollo Osseo; Gruppo Italiano Studio Linfomi; Hoffmann-La Roche
• Information provided by: Azienda Ospedaliera San Giovanni Battista

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Follicular Lymphoma	Procedure: High dose chemotherapy with autologous transplantation; Drug: Rituximab	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: MULTICENTER RANDOMIZED PROGRAM COMPARING HIGH-DOSE CHEMOTHERAPY + RITUXIMAB AND PERIPHERAL BLOOD PROGENITOR CELL (PBPC) AUTOGRAFT vs. CHOP + RITUXIMAB AS FIRST-LINE TREATMENT FOR PATIENTS WITH HIGH-RISK FOLLICULAR LYMPHOMA
• Study Start Date: March 2000

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Event free survival at three years

Secondary Outcome Measures :

1. Overall survival
2. CR rate
3. Progression free survival
4. Disease free survival I
5. Incidence of secondary myelodisplasia and solid cancer
6. Rate of molecular remission
7. Predictive value of molecular remission

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Italy

Divisione di Ematologia Universitaria

Torino, Italy, 10154

Sponsors and Collaborators

Azienda Ospedaliera San Giovanni Battista

University of Turin, Italy

Gruppo Italiano Trapianto di Midollo Osseo

Gruppo Italiano Studio Linfomi

Hoffmann-La Roche

Investigators

• Principal Investigator: Corrado Tarella, MD; Università di Torino, Azienda Ospedaliera San Giovanni Battista
• Principal Investigator: Marco Ladetto, MD; Università di Torino Azienda Ospedaliera San Giovanni Battista
• Principal Investigator: Alessandro Pileri, MD; Università di Torino Azienda Ospedaliera San Giovanni Battista (Now retired)
• Principal Investigator: Mario Boccadoro; Università di Torino/Azienda Ospedaliera San Giovanni Battista B
• Principal Investigator: Alessandro Gianni; Istituto Tumori di Milano, Milano Italy

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ladetto M, De Marco F, Benedetti F, Vitolo U, Patti C, Rambaldi A, Pulsoni A, Musso M, Liberati AM, Olivieri A, Gallamini A, Pogliani E, Rota Scalabrini D, Callea V, Di Raimondo F, Pavone V, Tucci A, Cortelazzo S, Levis A, Boccadoro M, Majolino I, Pileri A, Gianni AM, Passera R, Corradini P, Tarella C; Gruppo Italiano Trapianto di Midollo Osseo (GITMO); Intergruppo Italiano Linfomi (IIL). Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood. 2008 Apr 15;111(8):4004-13. doi: 10.1182/blood-2007-10-116749. Epub 2008 Jan 31.

• ClinicalTrials.gov Identifier: NCT00435955
• Other Study ID Numbers: 3320
• First Posted: February 16, 2007
• Last Update Posted: February 16, 2007
• Last Verified: February 2007

Keywords provided by Azienda Ospedaliera San Giovanni Battista:

Follicular lymphoma; age adjusted IPI >1; IIL score > 2; Molecular remission; High dose chemotherapy and autologous transplantation; Rituximab

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Follicular; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents