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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomised Trial Comparing Chemotherapy Mit CHOEP (Cyclophosphamid, Doxorubicin, Vincristin, Etoposid Und Prednison) In 21-Day Intervals In Standard And Escalated Doses In Patients Aged 18-60 Years Of Age With Aggresive Non-Hodgkin-Lymphomas Favourable Prognoses

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Drug: EPOCH regimen
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: prednisone
* Drug: vincristine sulfate
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CHOEP-21<br>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) | Biological: filgrastim<br> <br> Drug: EPOCH regimen<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: etoposide<br> <br> Drug: prednisone<br> <br> Drug: vincristine sulfate<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: high CHOEP-21<br>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) | Biological: filgrastim<br> <br> Drug: EPOCH regimen<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: etoposide<br> <br> Drug: prednisone<br> <br> Drug: vincristine sulfate<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure (TTF) at first relapse | Time to Treatment failure using the Kaplan_Meier-Method | 3 years within study and periodically after study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate at first relapse | Number of complete remission (CR) and unconfirmed complete Remission (CRu) | 3 years within study and periodically after study completion | 
| Survival time | Time till death (whatever cause) | 3 years within study and periodically after study completion | 
| Tumor control | Calcution of treatment Duration using the Kaplan-Meier method | thought the treatment | 
| Disease-free survival | Time of disease-free survivial | 3 years within study and periodically after study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, contiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, stage I adult diffuse mixed cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage IV adult diffuse mixed cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult Burkitt lymphoma, stage I adult diffuse large cell lymphoma, stage I adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult Burkitt lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, contiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, stage I adult lymphoblastic lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma