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

NCT00575406 | Completed Phase 2

• 2 other identifiers: NHL-14EudraCT 2007-004970-24
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 10

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).

Conditions

Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Reduction of cardiotoxicity in the R-COMP arm versus R-CHOP

  Study duration

Secondary Outcomes (7)

• 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

Study Arms (2)

R-CHOP

ACTIVE COMPARATOR

Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristin; Drug: Prednisolone

R-COMP

EXPERIMENTAL

Treatment with Rituximab, Cyclophosphamide, liposomal Doxorubicin, Vincristin and Prednisolone

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

Interventions

Rituximab DRUG

i.v., 375 mg/m2, d0 or d1 of each treatment cycle

Also known as: MabThera

R-CHOP; R-COMP

Cyclophosphamide DRUG

i.v., 750 mg/m2, d1 of each treatment cycle

Also known as: Cytoxan

R-CHOP; R-COMP

Doxorubicin DRUG

i.v., 50 mg/m2, d1 of each treatment cycle

Also known as: Adriamycin

R-CHOP

liposomal Doxorubicin DRUG

i.v., 50 mg/m2, d1 of each treatment cycle

Also known as: Myocet

R-COMP

Vincristin DRUG

i.v., 2mg, d1 of each treatment cycle

Also known as: Oncovin

R-CHOP; R-COMP

Prednisolone DRUG

p.o., 100mg, d1 - d5 of each treatment cycle

R-CHOP; R-COMP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arbeitsgemeinschaft medikamentoese Tumortherapie: lead

Study Sites (10)

Landeskrankenhaus Feldkirch

Feldkirch, A-6806, Austria

Location

Universitaetsklinik Innsbruck/ Klinik für Innere Medizin

Innsbruck, A-6020, Austria

Location

A.ö. Landeskrankenhaus Leoben

Leoben, A-8700, Austria

Location

Krankenhaus d. Barmherzigen Schwestern Linz

Linz, A-4010, Austria

Location

Krankenhaus der Elisabethinen Linz

Linz, A-4010, Austria

Location

Krankenhaus der Stadt Linz

Linz, A-4020, Austria

Location

Universitaetsklinik f. Innere Medizin III

Salzburg, A-5020, Austria

Location

AKH Wien / Haematologie u. Haemostaseologie

Vienna, A-1090, Austria

Location

Hanusch Krankenhaus

Vienna, A-1140, Austria

Location

Klinikum Kreuzschwestern Wels GmbH

Wels, A-4600, Austria

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; liposomal doxorubicin; Vincristine; Prednisolone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Michael A Fridrik, MD

  AKh Linz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2007
• First Posted: December 18, 2007
• Study Start: December 1, 2007
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: August 30, 2013

Record last verified: 2013-08

Locations

AU (10)