Clinical trial NCT00041132
Conditions: Lymphoma
Keywords: stage III mantle cell lymphoma stage IV mantle cell lymphoma contiguous stage II mantle cell lymphoma noncontiguous stage II mantle cell lymphoma
Sponsor: SWOG Cancer Research Network
Start date: 2002-09-01; Completion date: 2011-06-01
Enrollment: 56 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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. Combining rituximab with chemotherapy may kill more cancer cells.

PURPOSE: Phase II pilot study to study the effectiveness of combining chemotherapy with rituximab in treating patients who have newly diagnosed mantle cell lymphoma.

Detailed description:
OBJECTIVES:

* Determine the 1-year progression-free survival probability in patients with previously untreated mantle cell lymphoma treated with courses of rituximab and cyclophosphamide, doxorubicin, vincristine, and dexamethasone alternating with courses of rituximab and high-dose cytarabine and methotrexate with leucovorin calcium.
* Determine the response rate (complete unconfirmed and complete and partial responses) and survival of patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.
* Correlate chromosomal breakpoints, translocated immunoglobulin regulatory sequences, and cyclins D1, D2, and D3 with response and progression-free survival in patients treated with this regimen.
* Correlate gene expression (measured by DNA microarray analysis) with response and progression-free survival in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

* Courses 1, 3, 5, and 7: Patients receive rituximab IV on day 1 (courses 1, 3, and 5 only); cyclophosphamide IV over 3 hours twice a day on days 2-4; doxorubicin IV over 24 hours on days 5-7; vincristine IV on days 5 and 12; dexamethasone orally or IV four times a day on days 2-5 and 12-15; and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 8 and continuing until blood counts recover.
* Courses 2, 4, 6, and 8: Patients receive rituximab IV on day 1 (courses 2, 4, and 6 only); high-dose methotrexate IV over 24 hours on day 2; high-dose cytarabine IV over 2 hours twice a day on days 3-4; oral leucovorin calcium 4 times a day on days 3-10; and G-CSF SC daily beginning on day 5 and continuing until blood counts recover.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed within 30 days, every 3 months for 2 years, and then every 6 months for 3 years. Patients with disease progression are followed annually for up to 5 years from study entry.

PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study within 25 months.

Arms: arm 1: 21-day cycles of Hyper-CVAD and high-dose methotrexate/cytarabine are alternated beginning with Hyper-CVAD for a maximum of 8 cycles. Rituximab is given for cycles 1-6.

Hyper-CVAD (cycles 1,3,5,7): rituximab 375 mg/m\^2 on day 1, mesna 600 mg/m\^2 on days 2-4, cyclophosphamide 300 mg/m\^2 on days 2-4, doxorubicin 16.6 mg/m\^2/day on days 5-7, vincristine 1.4 mg/m\^2 on days 5 and 12, dexamethasone 40 mg on days 2-5 and 12-15, and filgrastim 5 ug/kg on days 8-21.

Methotrexate/Ara-C (cycles 2,4,6,8): rituximab 375 mg/m\^2 on day 1, methotrexate 1000 mg/m\^2 over days 2-3, Ara-C 12 g/m\^2 over days 3-4, leucovorin 170 mg over days 3-5, and G-CSF 5 ug/kg on days 5-21.
Interventions: intervention 1: filgrastim intervention 2: rituximab intervention 3: cyclophosphamide intervention 4: cytarabine intervention 5: dexamethasone intervention 6: doxorubicin intervention 7: leucovorin intervention 8: methotrexate intervention 9: vincristine
Intervention descriptions: intervention 1: 5 ug/kg intervention 2: 375 mg/m\^2 on day 1 of cycles 1-6 intervention 3: 300 mg/m\^2 on days 2-4 of cycles 1,3,5,7 intervention 4: 12 g/m\^2 over days 3-4 of cycles 2,4,6,8 intervention 5: 40 mg on days 2-5 and 12-15 of cycles 1,3,5,7 intervention 6: 16.6 mg/m\^2/day for days 5-7 of cycles 1,3,5,7 intervention 7: 170 mg over days 3-5 of cycles 2,4,6,8 intervention 8: 1000 mg/m\^2 over days 2-3 of cycles 2,4,6,8 intervention 9: 1.4 mg/m\^2 on days 5 and 12 of cycles 1,3,5,7

Protocol documents: