Rituximab, Prednisone, Cyclophosphamide, Doxorubicin, Vincristine, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Previously Untreated Mantle Cell Lymphoma

Study Overview
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Brief Summary
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RATIONALE: 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. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab and combination chemotherapy together with yttrium Y 90 ibritumomab tiuxetan works in treating patients with previously untreated mantle cell lymphoma.

Detailed Description
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OBJECTIVES: Determine the time to treatment failure in patients with previously untreated mantle cell lymphoma treated with rituximab and CHOP chemotherapy comprising prednisone, cyclophosphamide, doxorubicin, and vincristine followed by yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8; yttrium Y 90 Zevalin®). Determine the response rate in patients at the completion of rituximab and CHOP and the incremental response rate after IDEC-Y2B8. Determine the toxicity of this regimen in these patients. Correlate serum rituximab levels with response in patients treated with this regimen. OUTLINE: This is a multicenter study. CHOP chemotherapy and rituximab: Patients receive cyclophosphamide IV, doxorubicin IV, vincristine IV, and rituximab IV on day 1 and oral prednisone on days 1-5 (R + CHOP). Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who have responding or stable disease proceed to radioimmunotherapy. Radioimmunotherapy: Within 4-7 weeks after the completion of R + CHOP chemotherapy, patients receive rituximab IV and an imaging dose of indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients then undergo whole body gamma imaging scans during the first day (2-24 hours) and the second or third day (48-72 hours) after injection. In the absence of altered biodistribution, patients receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8; yttrium Y 90 Zevalin®) IV over 10 minutes on day 8. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years. PROJECTED ACCRUAL: A total of 57 patients will be accrued for this study within 2.8 years.

Official Title
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Phase II Study of Rituximab (NSC 687451) + CHOP Followed by 90Y-Ibritumomab Tiuxetan (NSC 710085) in Patients With Previously Untreated Mantle Cell 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: yttrium Y 90 ibritumomab tiuxetan


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed mantle cell lymphoma with expression of bcl-1 and CD20 Stage II-IV disease Measurable or evaluable disease Measurable disease defined as at least 1 bidimensionally measurable lesion at least 2 cm by imaging scan A spleen at least 17 cm or having discrete filling defects by CT scan will constitute evaluable disease provided that no explanation other than lymphomatous involvement (e.g., portal hypertension or other liver disease) is likely No known CNS lymphoma PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 6 months Hematopoietic WBC greater than 2,500/mm^3* Platelet count greater than 100,000/mm^3* NOTE: *Unless due to disease in bone marrow Hepatic Bilirubin less than 1.5 mg/dL (1.5-3.0 mg/dL if due to liver involvement by lymphoma) ALT and AST no greater than 2.5 times upper limit of normal (unless due to liver involvement by lymphoma) Renal Creatinine less than 2.0 mg/dL Calcium no greater than 11.5 mg/dL Cardiovascular LVEF greater than 45% Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 year after study participation HIV negative No other malignancy except treated carcinoma in situ of the cervix or squamous cell or basal cell skin cancer or any other surgically cured malignancy from which the patient has been disease-free for at least 3 years No other concurrent serious medical condition or active infection that would preclude ability to deliver standard prednisone, cyclophosphamide, doxorubicin, and vincristine (CHOP) chemotherapy PRIOR CONCURRENT THERAPY: Biologic therapy No prior immunotherapy Chemotherapy No prior chemotherapy Endocrine therapy Prior corticosteroids allowed provided the course was no more than 2 weeks in duration Radiotherapy No prior radiotherapy 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: rituximab|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: prednisone|nan|
|Drug: vincristine sulfate|nan|
|Radiation: yttrium Y 90 ibritumomab tiuxetan|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma