Combination Chemotherapy in Treating Patients With Newly Diagnosed Mantle Cell 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. PURPOSE: Phase II trial to study the effectiveness of different regimens of combination chemotherapy in treating patients with newly diagnosed mantle cell lymphoma.

Detailed Description
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OBJECTIVES: Evaluate the complete response rate and duration of response in patients with newly diagnosed diffuse or nodular mantle cell lymphoma or their blastic variant treated with high-dose methotrexate and cytarabine and high-dose cyclophosphamide, dexamethasone, doxorubicin, and vincristine (HCVAD). OUTLINE: This is a multicenter study. Patients may receive either regimen A or both regimen A and regimen B, depending upon response. Regimen A: Patients receive methotrexate IV over 24 hours on day 1. Cytarabine is administered IV over 2 hours every 12 hours on days 2 and 3. Filgrastim (G-CSF) is administered subcutaneously (SC) daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for up to 8 courses. Regimen B: Patients receive cyclophosphamide IV over 3 hours every 12 hours on days 1-3. Doxorubicin is administered IV over 24 hours on days 4 and 5. Vincristine is administered IV over 30 minutes on days 4 and 11. Dexamethasone is administered orally or IV on days 1-4 and 11-14. G-CSF is administered SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 7 courses. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 21-45 patients will be accrued for this study within 4 years.

Official Title
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Phase II CCOP Trial of High Dose Methotrexate/ARA-C and HCVAD for Newly Diagnosed Nodular and Diffuse Mantle Cell Lymphoma and Their Blastic Variants

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Drug: cyclophosphamide
* Drug: cytarabine
* Drug: dexamethasone
* Drug: doxorubicin hydrochloride
* Drug: methotrexate
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed previously untreated nodular or diffuse mantle cell lymphoma or their blastic variant No CNS involvement Not a candidate for stem cell transplantation or refuses one PATIENT CHARACTERISTICS: Age: 16 and over Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1,000/mm^3* Platelet count greater than 100,000/mm^3* NOTE: * Unless lymphoma involvement Hepatic: Bilirubin less than 1.5 mg/dL (unless lymphoma involvement) Renal: Creatinine less than 2.0 mg/dL (unless lymphoma involvement) Cardiovascular: Cardiac ejection fraction at least 50% (for patients over age 40) Other: Must be willing to receive blood transfusion Not pregnant or nursing Fertile patients must use effective contraception HIV negative No other co-morbid medical or psychiatric illness that would preclude treatment No prior or concurrent malignancy with poor prognosis (less than 90% probability of survival at 5 years) PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Minimum Age: 16 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A<br>Methotrexate IV over 24 hours on day 1. Cytarabine is administered IV over 2 hours every 12 hours on days 2 and 3. Filgrastim (G-CSF) is administered subcutaneously (SC) daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for up to 8 courses. | Biological: filgrastim<br> <br> Drug: cytarabine<br> <br> Drug: methotrexate<br> <br> |
| Experimental: Regimen B<br>Cyclophosphamide IV over 3 hours every 12 hours on days 1-3. Doxorubicin is administered IV over 24 hours on days 4 and 5. Vincristine is administered IV over 30 minutes on days 4 and 11. Dexamethasone is administered orally or IV on days 1-4 and 11-14. G-CSF is administered SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 7 courses. | Biological: filgrastim<br> <br> Drug: cyclophosphamide<br> <br> Drug: dexamethasone<br> <br> Drug: doxorubicin 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 |
| --- | --- | --- |

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