Multicentre Study to Determine the Cardiotoxicity of R-CHOP Compared to R-COMP in Patients With Diffuse Large B-Cell Lymphoma

Phase 2

Completed

• Conditions: Diffuse Large B-Cell Lymphoma
• Interventions: Drug: Rituximab; Drug: Cyclophosphamide; Drug: liposomal Doxorubicin; Drug: Doxorubicin; Drug: Vincristin; Drug: Prednisolone

• Registration Number: NCT00575406
• Lead Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2007-12
• Study First Submitted: 2007-12-17
• Study First Submitted QC: 2007-12-17
• Study First Posted: 2007-12-18
• Primary Completion: 2012-01
• Study Completion: 2012-01
• Status Verified: 2013-08
• Last Update Submitted: 2013-08-29
• Last Update Posted: 2013-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 94

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
R-CHOP	Rituximab	Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone
R-COMP	liposomal Doxorubicin	Treatment with Rituximab, Cyclophosphamide, liposomal Doxorubicin, Vincristin and Prednisolone
R-CHOP	Cyclophosphamide	Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone
R-CHOP	Doxorubicin	Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone
R-CHOP	Vincristin	Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone
R-CHOP	Prednisolone	Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone
R-COMP	Rituximab	Treatment with Rituximab, Cyclophosphamide, liposomal Doxorubicin, Vincristin and Prednisolone
R-COMP	Cyclophosphamide	Treatment with Rituximab, Cyclophosphamide, liposomal Doxorubicin, Vincristin and Prednisolone
R-COMP	Vincristin	Treatment with Rituximab, Cyclophosphamide, liposomal Doxorubicin, Vincristin and Prednisolone
R-COMP	Prednisolone	Treatment with Rituximab, Cyclophosphamide, liposomal Doxorubicin, Vincristin and Prednisolone

Primary Outcome Measures

Name	Time	Method
Reduction of cardiotoxicity in the R-COMP arm versus R-CHOP	Study duration

Secondary Outcome Measures

Name	Time	Method
Significance of serial NT-proBNP measurements for determination of anthracycline-dependent cardiotoxicity	Study Duration
Feasibility of evaluation with Haematopoietic Cell Transplantation Comorbidity Index (HCT-CI)	Study duration
Rate of Complete Responses	At end of treatment
Difference in Overall Survival at 3 and 5 yrs	5 years
Difference in Event-free Survival at 3 and 5 yrs	5 years
Difference in Progression-free Survival at 3 and 5 yrs	5 years
Difference in cause-specific death	5 years

Trial Locations

Locations (10)

Universitaetsklinik Innsbruck/ Klinik für Innere Medizin; 🇦🇹 Innsbruck, Austria

A.ö. Landeskrankenhaus Leoben; 🇦🇹 Leoben, Austria

Krankenhaus d. Barmherzigen Schwestern Linz; 🇦🇹 Linz, Austria

Krankenhaus der Stadt Linz; 🇦🇹 Linz, Austria

Hanusch Krankenhaus; 🇦🇹 Vienna, Austria

AKH Wien / Haematologie u. Haemostaseologie; 🇦🇹 Vienna, Austria

Krankenhaus der Elisabethinen Linz; 🇦🇹 Linz, Austria

Klinikum Kreuzschwestern Wels GmbH; 🇦🇹 Wels, Austria

Universitaetsklinik f. Innere Medizin III; 🇦🇹 Salzburg, Austria

Landeskrankenhaus Feldkirch; 🇦🇹 Feldkirch, Austria