Official Title: “Multicentre Study to Determine the Cardiotoxicity of R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone) Compared to R-COMP (Rituximab, Cyclophosphamide, Liposomal Doxorubicin, Vincristin and Prednisolone) in Patients With Diffuse Large B-Cell Lymphoma (NHL-14)”

Diffuse large B-cell lymphoma is the most prevalent subgroup within malignant lymphoma.

Clinical benefit has been shown for the treatment with cyclophosphamide, doxorubicin, vincristin and prednisolone (CHOP regimen); this could be further improved recently by the addition of rituximab (R-CHOP), a monoclonal antibody.

Improved response and overall survival rates make it necessary to evaluate late toxicities of the therapy regimens. Cardiotoxicity is a known risk factor of specific chemotherapies, with 7% patients being affected if doxorubicin cumulative doses are under 550mg/sqm. Retrospective data analyses indicate that this incidence of cardiotoxicity may be higher under combination chemotherapy. Liposomal doxorubicin has been shown to have lower cardiotoxic effects and at the same time equivalent or higher efficacy compared to conventional doxorubicin.

The aim of this study is to evaluate alternative regimens for the treatment of diffuse large B-cell lymphoma, substituting liposomal doxorubicin (R-COMP) for conventional doxorubicin (R-CHOP).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety Study

Primary:

• Reduction of cardiotoxicity in the R-COMP arm versus R-CHOP Study duration Yes

Secondary:

• Significance of serial NT-proBNP measurements for determination of anthracycline-dependent cardiotoxicity Study Duration Yes
• Feasibility of evaluation with Haematopoietic Cell Transplantation Comorbidity Index (HCT-CI) Study duration Yes
• Rate of Complete Responses At end of treatment No
• Difference in Overall Survival at 3 and 5 yrs 5 years No
• Difference in Event-free Survival at 3 and 5 yrs 5 years No
• Difference in Progression-free Survival at 3 and 5 yrs 5 years No
• Difference in cause-specific death 5 years No

Inclusion Criteria:

• Histologically confirmed, CD20 positive, diffuse large B-cell lymphoma (DLCL)
• measurable disease according to international criteria
• male or female
• age 18 years and above
• written informed consent

Exclusion Criteria:

• myocardial infarction within 6 months prior to study entry
• cardiac insufficiency NYHA grade 3 or 4
• previous treatment with chemotherapy or radiotherapy
• CNS involvement of the disease
• positive for HIV
• WHO Performance Index 3 or 4
• secondary malignoma
• concurrent disease that prohibits chemotherapy
• known hypersensitivity towards the study interventions or their constituents
• neutropenia or thrombopenia

Lead Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie

A.ö. Landeskrankenhaus Leoben

Leoben  A-8700 Austria

AKH Wien / Haematologie u. Haemostaseologie

Vienna  A-1090 Austria

Hanusch Krankenhaus

Vienna  A-1140 Austria

Klinikum Kreuzschwestern Wels GmbH

Wels  A-4600 Austria

Krankenhaus d. Barmherzigen Schwestern Linz

Linz  A-4010 Austria

Krankenhaus der Elisabethinen Linz

Linz  A-4010 Austria

Krankenhaus der Stadt Linz

Linz  A-4020 Austria

Landeskrankenhaus Feldkirch

Feldkirch  A-6806 Austria

Universitaetsklinik f. Innere Medizin III

Salzburg  A-5020 Austria

Universitaetsklinik Innsbruck/ Klinik für Innere Medizin

Innsbruck  A-6020 Austria

Overall Clinical Trial Officials and Contacts

Michael A Fridrik, MD Principal Investigator AKh Linz  

Overall Contact: Michael A Fridrik, MD +437327806 michael.fridrik@akh.linz.at

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00575406

Study ID Number: NHL-14

ClinicalTrials.gov Identifier: NCT00575406

Health Authority: Austria: Federal Office for Safety in Health Care