Multicentre Study to Determine the Cardiotoxicity of R-CHOP Compared to R-COMP in Patients With Diffuse Large B-Cell Lymphoma (NHL-14)

• 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 ]

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).

• Drug: Rituximab
  i.v., 375 mg/m2, d0 or d1 of each treatment cycle
  Other Name: MabThera
• Drug: Cyclophosphamide
  i.v., 750 mg/m2, d1 of each treatment cycle
  Other Name: Cytoxan
• Drug: Doxorubicin
  i.v., 50 mg/m2, d1 of each treatment cycle
  Other Name: Adriamycin
• Drug: liposomal Doxorubicin
  i.v., 50 mg/m2, d1 of each treatment cycle
  Other Name: Myocet
• Drug: Vincristin
  i.v., 2mg, d1 of each treatment cycle
  Other Name: Oncovin
• Drug: Prednisolone
  p.o., 100mg, d1 - d5 of each treatment cycle

• Active Comparator: R-CHOP
  Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone
  Interventions:

  • Drug: Rituximab
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Vincristin
  • Drug: Prednisolone
• Experimental: R-COMP
  Treatment with Rituximab, Cyclophosphamide, liposomal Doxorubicin, Vincristin and Prednisolone
  Interventions:

  • Drug: Rituximab
  • Drug: Cyclophosphamide
  • Drug: liposomal Doxorubicin
  • Drug: Vincristin
  • Drug: Prednisolone

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