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

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

Overview[ - collapse ][ - ]

Purpose	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).
Condition	Diffuse Large B-Cell Lymphoma
Intervention	Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: liposomal Doxorubicin Drug: Vincristin Drug: Prednisolone
Phase	Phase 2
Sponsor	Arbeitsgemeinschaft medikamentoese Tumortherapie
Responsible Party	Arbeitsgemeinschaft medikamentoese Tumortherapie
ClinicalTrials.gov Identifier	NCT00575406
First Received	December 17, 2007
Last Updated	August 29, 2013
Last verified	August 2013

Tracking Information[ + expand ][ + ]

First Received Date	December 17, 2007
Last Updated Date	August 29, 2013
Start Date	December 2007
Estimated Primary Completion Date	January 2012
Current Primary Outcome Measures	Reduction of cardiotoxicity in the R-COMP arm versus R-CHOP [Time Frame: Study duration] [Designated as safety issue: Yes]
Current Secondary Outcome Measures	Significance of serial NT-proBNP measurements for determination of anthracycline-dependent cardiotoxicity [Time Frame: Study Duration] [Designated as safety issue: Yes] Feasibility of evaluation with Haematopoietic Cell Transplantation Comorbidity Index (HCT-CI) [Time Frame: Study duration] [Designated as safety issue: Yes] Rate of Complete Responses [Time Frame: At end of treatment] [Designated as safety issue: No] Difference in Overall Survival at 3 and 5 yrs [Time Frame: 5 years] [Designated as safety issue: No] Difference in Event-free Survival at 3 and 5 yrs [Time Frame: 5 years] [Designated as safety issue: No] Difference in Progression-free Survival at 3 and 5 yrs [Time Frame: 5 years] [Designated as safety issue: No] Difference in cause-specific death [Time Frame: 5 years] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	Multicentre Study to Determine the Cardiotoxicity of R-CHOP Compared to R-COMP in Patients With Diffuse Large B-Cell Lymphoma
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)
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 Provided
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Diffuse Large B-Cell Lymphoma
Intervention	Drug: Rituximab i.v., 375 mg/m2, d0 or d1 of each treatment cycle Other Names: MabTheraDrug: Cyclophosphamide i.v., 750 mg/m2, d1 of each treatment cycle Other Names: CytoxanDrug: Doxorubicin i.v., 50 mg/m2, d1 of each treatment cycle Other Names: AdriamycinDrug: liposomal Doxorubicin i.v., 50 mg/m2, d1 of each treatment cycle Other Names: MyocetDrug: Vincristin i.v., 2mg, d1 of each treatment cycle Other Names: OncovinDrug: Prednisolone p.o., 100mg, d1 - d5 of each treatment cycle
Study Arm (s)	Active Comparator: R-CHOP Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone Experimental: R-COMP Treatment with Rituximab, Cyclophosphamide, liposomal Doxorubicin, Vincristin and Prednisolone

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	94
Estimated Completion Date	January 2012
Estimated Primary Completion Date	January 2012
Eligibility Criteria	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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Austria

Administrative Information[ + expand ][ + ]

NCT Number	NCT00575406
Other Study ID Numbers	NHL-14
Has Data Monitoring Committee	No
Information Provided By	Arbeitsgemeinschaft medikamentoese Tumortherapie
Study Sponsor	Arbeitsgemeinschaft medikamentoese Tumortherapie
Collaborators	Not Provided
Investigators	Principal Investigator: Michael A Fridrik, MD AKh Linz
Verification Date	August 2013

Locations[ + expand ][ + ]

Landeskrankenhaus Feldkirch	Feldkirch, Austria, A-6806
Universitaetsklinik Innsbruck/ Klinik für Innere Medizin	Innsbruck, Austria, A-6020
A.ö. Landeskrankenhaus Leoben	Leoben, Austria, A-8700
Krankenhaus der Elisabethinen Linz	Linz, Austria, A-4010
Krankenhaus d. Barmherzigen Schwestern Linz	Linz, Austria, A-4010
Krankenhaus der Stadt Linz	Linz, Austria, A-4020
Universitaetsklinik f. Innere Medizin III	Salzburg, Austria, A-5020
Hanusch Krankenhaus	Vienna, Austria, A-1140
AKH Wien / Haematologie u. Haemostaseologie	Vienna, Austria, A-1090
Klinikum Kreuzschwestern Wels GmbH	Wels, Austria, A-4600