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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: liposomal Doxorubicin
* Drug: Vincristin
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: R-CHOP<br>Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone | Drug: Rituximab<br>* i.v., 375 mg/m2, d0 or d1 of each treatment cycle<br>* Other names: MabThera;Drug: Cyclophosphamide<br>* i.v., 750 mg/m2, d1 of each treatment cycle<br>* Other names: Cytoxan;Drug: Doxorubicin<br>* i.v., 50 mg/m2, d1 of each treatment cycle<br>* Other names: Adriamycin;Drug: Vincristin<br>* i.v., 2mg, d1 of each treatment cycle<br>* Other names: Oncovin;Drug: Prednisolone<br>* p.o., 100mg, d1 - d5 of each treatment cycle<br>|
| Experimental: R-COMP<br>Treatment with Rituximab, Cyclophosphamide, liposomal Doxorubicin, Vincristin and Prednisolone | Drug: Rituximab<br>* i.v., 375 mg/m2, d0 or d1 of each treatment cycle<br>* Other names: MabThera;Drug: Cyclophosphamide<br>* i.v., 750 mg/m2, d1 of each treatment cycle<br>* Other names: Cytoxan;Drug: liposomal Doxorubicin<br>* i.v., 50 mg/m2, d1 of each treatment cycle<br>* Other names: Myocet;Drug: Vincristin<br>* i.v., 2mg, d1 of each treatment cycle<br>* Other names: Oncovin;Drug: Prednisolone<br>* p.o., 100mg, d1 - d5 of each treatment cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of cardiotoxicity in the R-COMP arm versus R-CHOP |  | Study duration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |