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Combination Chemotherapy Followed By Radiation Therapy in Treating Patients With Aggressive Non-Hodgkin's Lymphoma

Phase 3
Completed
Conditions
Lymphoma
Interventions
Registration Number
NCT00053768
Lead Sponsor
German High-Grade Non-Hodgkin's Lymphoma Study Group
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and giving the drugs in different ways may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known which combination chemotherapy regimen followed by radiation therapy is more effective in treating aggressive non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens followed by radiation therapy to compare how well they work in treating patients with aggressive non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

* Compare the efficacy of standard-dose vs high-dose cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone followed by radiotherapy, in terms of time to treatment failure, in patients with aggressive non-Hodgkin's lymphoma.

* Compare the acute and long-term toxic effects of these regimens in these patients.

* Compare the complete response rate, survival and tumor control, and disease-free survival in patients treated with these regimens.

* Analyze the time to relapse after radiotherapy in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to LDH levels (no greater than upper limit of normal \[ULN\] vs greater than ULN), initial bulky disease (yes vs no), stage (I or II vs II or IV), ECOG performance status (0 or 1 vs 2 or 3), and participating center. Patients are randomized to 1 of 2 treatment arms as follows:

* Arm I (Standard dose): Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; etoposide IV on days 1-3; and oral prednisone on days 1-5 (CHOEP) in standard doses.

* Arm II (Escalated dose): Patients receive high-dose CHOEP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously on days 6-12.

In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of CHOEP chemotherapy, patients with initial bulky disease or extranodal involvement undergo radiotherapy 5 days a week for 4 weeks.

Patients who undergo radiotherapy are followed at 2 months after radiotherapy. All patients (including those who undergo radiotherapy) are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 389 patients were accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
392
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
high CHOEP-21vincristine sulfateHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21EPOCH regimenCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21filgrastimCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21EPOCH regimenHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21radiation therapyHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21vincristine sulfateCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21radiation therapyCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21filgrastimHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21doxorubicin hydrochlorideCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21cyclophosphamideCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21etoposideCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21prednisoneCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21cyclophosphamideHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21doxorubicin hydrochlorideHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21prednisoneHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21etoposideHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
Primary Outcome Measures
NameTimeMethod
Time to treatment failure (TTF) at first relapse3 years within study and periodically after study completion

Time to Treatment failure using the Kaplan_Meier-Method

Secondary Outcome Measures
NameTimeMethod
Tumor controlthought the treatment

Calcution of treatment Duration using the Kaplan-Meier method

Complete response rate at first relapse3 years within study and periodically after study completion

Number of complete remission (CR) and unconfirmed complete Remission (CRu)

Survival time3 years within study and periodically after study completion

Time till death (whatever cause)

Disease-free survival3 years within study and periodically after study completion

Time of disease-free survivial

Trial Locations

Locations (165)

Haematologisch Onkologische Praxis

🇩🇪

Aachen, Germany

Klinikum St. Marien

🇩🇪

Amberg, Germany

Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie

🇩🇪

Ansbach, Germany

Specialist Practice for Oncology

🇩🇪

Aschaffenburg, Germany

II. Medizinische Klinik

🇩🇪

Aschaffenburg, Germany

Haematologische Praxis

🇩🇪

Augsburg, Germany

Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg

🇩🇪

Augsburg, Germany

Klinikum Augsburg

🇩🇪

Augsburg, Germany

Kreiskrankenhaus Aurich

🇩🇪

Aurich, Germany

Kreiskrankenhaus

🇩🇪

Bad Hersfeld, Germany

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Haematologisch Onkologische Praxis
🇩🇪Aachen, Germany

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