S0313 Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Radiation Therapy Followed By Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan 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, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Monoclonal antibodies, such as rituximab and yttrium Y 90 ibritumomab tiuxetan, can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining chemotherapy with radiation therapy and monoclonal antibody therapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy and monoclonal antibody therapy works in treating patients with stage I or stage II non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the 2-year progression-free survival of patients with aggressive high-risk stage I or IE or non-bulky stage II or IIE CD20-positive non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone and radiotherapy followed by rituximab and yttrium Y 90 ibritumomab tiuxetan. Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Chemotherapy: Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 1-2 hours, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Radiotherapy: Beginning 3 weeks after the completion of CHOP chemotherapy, patients undergo radiotherapy once daily 5 days a week for 4-5 weeks. Monoclonal antibody therapy: Beginning 3-6 weeks after the completion of radiotherapy, patients receive rituximab IV followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients then undergo whole body imaging. If ibritumomab tiuxetan biodistribution is acceptable, patients receive rituximab IV and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7, 8, OR 9. Patients are followed every 6 months for 2 years and then annually thereafter. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 15 months.

Official Title
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Evaluation of CHOP Plus Involved Field Radiotherapy Followed by Yttrium-90 Ibritumomab Tiuxetan for Stages I, IE, and Non-Bulky Stages II and IIE, CD20 Positive, High-Risk Localized, Aggressive Histologies of Non-Hodgkin Lymphoma, Phase II

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
* Biological: Yttrium-90 ibritumomab tiuxetan
* Biological: Indium-111 ibritumomab tiuxetan


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 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) Stage I, IE, or non-bulky* stage II or IIE disease by Ann Arbor classification Patients who have bulky stage II or IIE disease are ineligible even if, after resection, the measurements are less than 10.0 cm NOTE: *Non-bulky disease defined as any tumor measuring less than 10.0 cm or occupying less than 1/3 of the chest diameter CD20-expressing disease by flow cytometry or immunoperoxidase staining Aggressive lymphomas must have at least 1 of the following adverse prognostic factors: Non-bulky stage II or IIE disease At least 60 years of age Zubrod performance status of 2 Lactic dehydrogenase greater than upper limit of normal All disease must be encompassable in a single radiation port (including any site of resected disease) NOTE: 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 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No medical contraindication to study chemotherapy, rituximab, or ibritumomab tiuxetan No known AIDS syndrome or HIV-associated complex PRIOR CONCURRENT THERAPY: Biologic therapy No prior monoclonal antibody therapy Chemotherapy No prior chemotherapy for lymphoma Endocrine therapy Not specified Radiotherapy See Disease Characteristics No prior radiotherapy for lymphoma No concurrent intensity-modulated radiotherapy Planned involved-field radiotherapy must not encompass more than 25% of active bone marrow space Surgery See Disease Characteristics Other Concurrent participation in SWOG-8947 or SWOG-8819 allowed

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 + RT + Zevalin<br>Patients first receive 3 cycles (21 days each) of CHOP, consisting of: cyclophosphamide 750 mg/m^2 on day 1, doxorubicin 50 mg/m^2 on day 1, vincristine 1.4 mg/m^2 on day 1, and prednisone 100 mg on days 1-5. Patients receive 4000-5000 cGy of radiation therapy in 25 fractions, starting 3 weeks after completion of CHOP. 3-6 weeks after completing RT, patients receive Zevalin, which consists of: rituximab 250 mg/m^2 on days 1 and 7, 8 or 9; In-111 ibritumomab tiuxetan 5 mCi within 4 hours after rituximab on day 1; and Y-90 ibritumomab tiuxetan 0.4 mCi/kg within 4 hours after rituximab on day 7, 8 or 9. | Biological: rituximab<br>* 250 mg/m^2, as part of Zevalin regimen<br>Drug: Cyclophosphamide<br>* 750 mg/m^2<br>Drug: doxorubicin hydrochloride<br>* 50 mg/m^2<br>Drug: prednisone<br>* 100 mg<br>Drug: vincristine sulfate<br>* 1.4 mg/m^2<br>Radiation: radiation therapy<br>* 4000-5000 cGy total<br>Biological: Yttrium-90 ibritumomab tiuxetan<br>* 0.4 mCi/kg<br>Biological: Indium-111 ibritumomab tiuxetan<br>* 5 mCi<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Measured from date of registration to date of first observation of progression or symptomatic deterioration. Progression is defined as one or more of the following must occur. Unequivocal progression of disease in the opinion of the treating physician (an explanation must be provided). Appearance of a new lesion/site. Death due to disease without documented progression or symptomatic deterioration. Symptomatic deterioration is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. | at 6 weeks after 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 mantle cell lymphoma, stage I adult diffuse large cell lymphoma, stage I adult Burkitt lymphoma, anaplastic large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult Burkitt lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II mantle cell lymphoma