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

Sponsor

Arbeitsgemeinschaft medikamentoese Tumortherapie (Other)

Overall Status

Completed

CT.gov ID

NCT00575406

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

9.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-Cell Lymphoma	Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: liposomal Doxorubicin Drug: Vincristin Drug: Prednisolone	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

94 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Study Start Date :

Dec 1, 2007

Actual Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: R-CHOP

Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin and Prednisolone

Drug: Rituximab

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

Other Names:

MabThera

Drug: Cyclophosphamide

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

Other Names:

Cytoxan

Drug: Doxorubicin

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

Other Names:

Adriamycin

Drug: Vincristin

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

Other Names:

Oncovin

Drug: Prednisolone

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

Experimental: R-COMP

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

Drug: Rituximab

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

Other Names:

MabThera

Drug: Cyclophosphamide

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

Other Names:

Cytoxan

Drug: liposomal Doxorubicin

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

Other Names:

Myocet

Drug: Vincristin

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

Other Names:

Oncovin

Drug: Prednisolone

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

Outcome Measures

Primary Outcome Measures

Reduction of cardiotoxicity in the R-COMP arm versus R-CHOP [Study duration]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Landeskrankenhaus Feldkirch	Feldkirch	Austria	A-6806
2	Universitaetsklinik Innsbruck/ Klinik für Innere Medizin	Innsbruck	Austria	A-6020
3	A.ö. Landeskrankenhaus Leoben	Leoben	Austria	A-8700
4	Krankenhaus d. Barmherzigen Schwestern Linz	Linz	Austria	A-4010
5	Krankenhaus der Elisabethinen Linz	Linz	Austria	A-4010
6	Krankenhaus der Stadt Linz	Linz	Austria	A-4020
7	Universitaetsklinik f. Innere Medizin III	Salzburg	Austria	A-5020
8	AKH Wien / Haematologie u. Haemostaseologie	Vienna	Austria	A-1090
9	Hanusch Krankenhaus	Vienna	Austria	A-1140
10	Klinikum Kreuzschwestern Wels GmbH	Wels	Austria	A-4600