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

Study Primary Completion Date: March 2013

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

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

Primary Measures

• Reduction of cardiotoxicity in the R-COMP arm versus R-CHOP
  • Time Frame: Study duration
    Safety Issue?: Yes

Secondary Measures

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie

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 02, 2009

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