Combination Chemotherapy 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. It is not yet known which regimen of combination chemotherapy is most effective for non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying two regimens of combination chemotherapy and comparing how well they work in treating patients with aggressive non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Compare the overall survival, failure free survival, disease specific survival, relapse free survival, and response rate in patients with aggressive non-Hodgkin's lymphoma treated with mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone (PMitCEBO) versus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Compare the early and late toxicities of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive mitoxantrone IV, cyclophosphamide IV, and etoposide IV on day 1 and vincristine and bleomycin IV on day 8. Treatment continues every 14 days for a maximum of 8 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral prednisolone daily on courses 1 and 2 and every other day beginning on course 3 and continuing until the end of treatment. Arm II: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Treatment continues every 21 days for a maximum of 8 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 4 weeks, then every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 310 patients (155 per arm) will be accrued for this study over 5 years.

Official Title
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Phase III Trial Comparing CHOP ot PMitCEBO in Good Risk Patients With Histologically Aggresive Non Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: bleomycin sulfate
* Drug: CHOP regimen
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: mitoxantrone hydrochloride
* Drug: prednisolone
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven previously untreated bulky stage IA or stage IB-IV aggressive non-Hodgkin's lymphoma of 1 of the following types: Working formulation: Follicular large cell Diffuse mixed cell Diffuse large cell Diffuse immunoblastic OR REAL classification: Diffuse large B-cell Peripheral T-cell Measurable or evaluable disease Good prognosis defined as no more than one of the following: Stage III/IV disease LDH greater than upper limit of normal ECOG/WHO 2-4 No lymphoblastic or Burkitt's lymphoma No CNS involvement PATIENT CHARACTERISTICS: Age: 18 to 59 Performance status: See Disease Characteristics Life expectancy: Not specified Hematopoietic: Hemoglobin at least 10 g/dL Neutrophil count at least 2,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin, AST, and ALT no greater than 1.5 times upper limit of normal Renal: Creatinine no greater than 1.7 mg/dL Cardiovascular: Ejection fraction at least 50% unless dysfunction attributable to lymphoma Other: Not pregnant or nursing Fertile patients must use effective contraception No other concurrent serious uncontrolled medical conditions No other prior malignancy except adequately treated nonmelanoma skin cancer or cervical intraepithelial neoplasia PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to more than 35% of hematopoietic sites Concurrent consolidation radiotherapy allowed Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bleomycin sulfate|nan|
|Drug: CHOP regimen|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: etoposide|nan|
|Drug: mitoxantrone hydrochloride|nan|
|Drug: prednisolone|nan|
|Drug: vincristine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival in patients treated with mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone (PMitCEBO) versus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival, disease specific survival, relapse-free survival, death due to toxicity, response rate, and toxicity at 4 years |  |  | 

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