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

German High-Grade Non-Hodgkin's Lymphoma Study Group

Status and phase: Completed; Phase 3

Conditions: Lymphoma

Treatments: Drug: cyclophosphamide; Drug: prednisone; Drug: EPOCH regimen; Biological: filgrastim; Drug: doxorubicin hydrochloride; Radiation: radiation therapy; Drug: etoposide; Drug: vincristine sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT00053768

EU-20242

DSHNHL-1999-2

CDR0000269371

Details and patient eligibility

About

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.

Full 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.

Enrollment: 392 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin's lymphoma

  • Previously untreated disease

• Favorable prognosis

  • International Prognostic Index score of 0-1

• No more than 25% marrow involvement

PATIENT CHARACTERISTICS:

Age

• 18 to 60

Performance status

• ECOG 0-3 OR
• Karnofsky 40-100%

Life expectancy

• Not specified

Hematopoietic

• Platelet count at least 100,000/mm^3
• WBC at least 2,500/mm^3

Hepatic

• No active hepatitis infection

Renal

• Not specified

Other

• HIV negative
• Not pregnant or nursing
• No relevant accompanying disease
• No other concurrent malignancy
• No contraindications to any study medications
• No prior noncompliance by patient

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• No other concurrent participation in another treatment study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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392 participants in 2 patient groups

CHOEP-21

Active Comparator group

Description:

CHOEP-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)

Treatment:

Drug: EPOCH regimen

Drug: vincristine sulfate

Drug: etoposide

Drug: prednisone

Biological: filgrastim

Radiation: radiation therapy

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

high CHOEP-21

Experimental group

Description:

High-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)

Treatment:

Drug: EPOCH regimen

Drug: vincristine sulfate

Drug: etoposide

Drug: prednisone

Biological: filgrastim

Radiation: radiation therapy

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride