Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV 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 may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating stage III or stage IV Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have stage III or stage IV Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Compare event-free survival of patients with stage III or IV Hodgkin's lymphoma treated with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone vs doxorubicin, bleomycin, vinblastine, and dacarbazine. Compare complete response, disease-free survival, and overall survival of patients treated with these regimens. Compare quality of life of patients treated with these regimens. Compare occurrence of second malignancies in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to International Prognostic Score (3 vs 4 or more) and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I (BEACOPP): Patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV on day 1; etoposide IV over 30 minutes on days 1-3; oral procarbazine on days 1-7; oral prednisone on days 1-14; and vincristine IV and bleomycin IV or intramuscularly (IM) on day 8. Patients may receive dexamethasone in place of prednisone. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 9 and continuing until blood counts recover or pegfilgrastim SC on day 9 only. Treatment repeats every 22 days for 8 courses (4 courses escalated dose followed by 4 courses baseline dose) in the absence of disease progression or unacceptable toxicity. Arm II (ABVD): Patients receive doxorubicin IV over 5 minutes, bleomycin IV or IM, vinblastine IV, and dacarbazine IV over 5-10 minutes on days 1 and 15. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at the end of therapy, and then annually for 10 years. Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 550 patients (225 per treatment arm) will be accrued for this study within 5.5 years.

Official Title
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BEACOPP (4 Cycles Escalated + 4 Cycles Baseline) Versus ABVD (8 Cycles) In Stage III & IV Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: bleomycin sulfate
* Biological: filgrastim
* Biological: pegfilgrastim
* Drug: ABVD regimen
* Drug: BEACOPP regimen
* Drug: cyclophosphamide
* Drug: dacarbazine
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: prednisone
* Drug: procarbazine hydrochloride
* Drug: vinblastine sulfate
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed Hodgkin's lymphoma No lymphocyte predominant, nodular type (nodular paragranuloma) Clinical stage III or IV disease At least 1 bidimensionally measurable target lesion or extranodal lesion International Prognostic Score of at least 3 PATIENT CHARACTERISTICS: Age 16 to 60 Performance status WHO 0-2 Life expectancy Not specified Hematopoietic WBC greater than 2,000/mm^3 Platelet count greater than 100,000/mm^3 Hepatic No prior uncontrolled hepatitis B viral infection Bilirubin no greater than 2.5 times normal (unless due to Hodgkin's lymphoma) Renal Creatinine no greater than 2.0 mg/dL (unless due to Hodgkin's lymphoma) Cardiovascular No severe cardiac disease that would limit normal life expectancy or preclude study LVEF at least 50% Pulmonary No severe pulmonary disease that would limit normal life expectancy or preclude study Respiratory function at least 30% Other HIV negative HTLV1 negative No severe active infection No severe neurological or metabolic disease that would limit normal life expectancy or preclude study No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix No psychological, familial, sociological, or geographical condition that would preclude study Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy No concurrent radiotherapy Surgery Not specified Other No prior therapy for Hodgkin's lymphoma

Ages Eligible for Study
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Minimum Age: 16 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: ABVD<br>8 cycles of ABVD | Biological: bleomycin sulfate<br> <br> Drug: ABVD regimen<br> <br> Drug: dacarbazine<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: vinblastine sulfate<br> <br> |
| Experimental: BEACOPP<br>4 cycles of BEACOPP Escalated + 4 cycles of BEACOPP Baseline | Biological: bleomycin sulfate<br> <br> Biological: filgrastim<br> <br> Biological: pegfilgrastim<br> <br> Drug: BEACOPP regimen<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: etoposide<br> <br> Drug: prednisone<br> <br> Drug: procarbazine hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival |  | from randomization to early discontinuation of protocol treatment, no CR/CRu after 8 cycles, relapse, progression or death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response as assessed by Cheson criteria adapted to Hodgkin's lymphoma |  | from randomization till end of treatment | 
| Disease-free survival in patients with complete response |  | from the day of first documentation of CR to the day of relapse | 
| Overall survival |  | from the date of randomization to the date of death | 
| Quality of life as assessed by European Organization for Research of the Treatment of Cancer (EORTC) Quality of Life Questionnaire (QoLQ) C30 version 3.0 |  | from one week prior to randomization till 10 years after end of treatment or death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult lymphocyte depletion Hodgkin lymphoma, adult mixed cellularity Hodgkin lymphoma, adult nodular sclerosis Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma