S0014 Combination Chemotherapy Plus Rituximab and Radiation Therapy in Treating Patients With Stage I or Stage II 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. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy with monoclonal antibody therapy and radiation therapy may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus rituximab and radiation therapy in treating patients who have stage I or stage II non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: I. Assess two year progression free survival after treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab followed by radiotherapy in patients with stage I, IE, or non-bulky stage II or IIE high risk localized intermediate or high grade non-Hodgkin's lymphoma. II. Determine the toxicity of this treatment in these patients. OUTLINE: Patients receive rituximab IV on days 1 and 8 of the first course, then on day 1 of courses 2 and 3. Patients receive cyclophosphamide IV over 1-2 hours, doxorubicin IV, and vincristine IV on day 10 of the first course, then on day 3 of courses 2 and 3. Patients receive oral prednisone on days 10-14 of the first course, then on days 3-7 of courses 2 and 3. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Chemotherapy is followed by radiotherapy administered 5 days a week for 4-5 weeks. Patients are followed every 6 months for two years, and then annually thereafter. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Official Title
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Evaluation of CHOP Plus Rituximab Plus Involved Field Radiotherapy for Stages I, IE, and Non-Bulky Stages II and IIE, CD20 Positive, High-Risk Localized Aggressive Histologies of Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage I, IE, or non-bulky II or IIE non-Hodgkin's lymphoma of one of the following subtypes: Diffuse large B-cell Mantle cell High grade B-cell, Burkitt's or Burkitt like Anaplastic large cell (B-cell phenotype only) Lymphoma must express CD20 All disease must be encompassable in a single radiation port (including any resected disease) Must have at least 1 of the following adverse prognostic features: Non-bulky stage II or non-bulky stage IIE disease Over 60 years of age Zubrod performance status of 2 Elevated serum LDH A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of indolent or aggressive lymphoma will replace the former terminology of low, intermediate, or high grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: No medical contraindications to CHOP chemotherapy or rituximab No prior malignancy within past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No AIDS or HIV Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior monoclonal antibody therapy Chemotherapy: No prior chemotherapy for lymphoma Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy for lymphoma Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHOP + Rituximab + RT<br>3 21-day cycles of CHOP (cyclophosphamide 750 mg/m^2, doxorubicin 50 mg/m^2, vincristine 1.4 mg/m^2, prednisone 100 mg x 5 days) + Rituximab 375 mg/m^2 (x 2 days for cycle 1, x 3 days for cycles 2-3). RT 4000-5500 cGy given in 25 fractions starting 3 weeks after completion of CHOP + Rituximab. | Biological: rituximab<br>* 375 mg/m^2 on days 1,8 of cycle 1, then on days 1-3 of cycles 2-3.<br>Drug: cyclophosphamide<br>* 750 mg/m^2 on day 10 of cycle 1, then on day 21 of cycles 2-3.<br>Drug: doxorubicin hydrochloride<br>* 50 mg/m^2 on day 10 of cycle 1, then on day 21 of cycles 2-3.<br>Drug: prednisone<br>* 100 mg on days 10-14 of cycle 1, then on days 3-7 of cycles 2-3.<br>Drug: vincristine sulfate<br>* 1.4 mg/m^2 on day 10 of cycle 1, then on day 3 of cycles 2-3.<br>Radiation: radiation therapy<br>* 4000-5500 cGy given in 25 fractions starting 3 weeks after completion of CHOP + Rituximab.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | every 6 weeks while on protocol treatment, then every 6 months for 2 years, then annually thereafter | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I adult diffuse large cell lymphoma, stage I adult Burkitt lymphoma, stage I mantle cell lymphoma, contiguous stage II mantle cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult Burkitt lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult Burkitt lymphoma