R-MACLO-IVAM and Thalidomide in Untreated Mantle Cell Lymphoma

OBJECTIVES:

Primary

- Determine the progression-free survival of patients with previously untreated mantle
cell lymphoma treated rituximab in combination with methotrexate, doxorubicin,
cyclophosphamide, leucovorin, vincristine, ifosfamide, etoposide, cytarabine and mesna
(MACLO/IVAM) followed by thalidomide.

Secondary

- Determine the overall survival of patients treated with this regimen.

- Determine the response rate in patients treated with this regimen.

- Determine the toxicity of this regimen in these patients.

OUTLINE: During cycle 1, patients will receive rituximab intravenous (IV), granisetron IV,
decadron IV, doxorubicin IV bolus, vincristine intravenous pyelogram (IVP) on day 1;
cyclophosphamide IV on day 1-5; vincristine IVP on day 8; methotrexate IV, methotrexate by
continuous infusion, then leucovorin IV until methotrexate level is below 0.01 nanomolar
(nM) on day 10. Patients will receive filgrastim (G-CSF) subcutaneously (SC) once daily
beginning on day 13 and continuing until blood counts recover.

When absolute neutrophil count (ANC) reaches1,500/mm^3, patients will start cycle 2.
Patients will receive rituximab IV on day 1; cytarabine IV on day 1 and 2; ifosfamide IV,
mesna IV, etoposide IV on day 1-5; and G-CSF SC daily beginning on day 7 and continuing
until ANC is greater than 1,000 cells/mm^3.

Approximately 2-3 weeks later, patients receive another course of therapy as above.After
cycle 4, patients in complete remission will take oral thalidomide until progression of
disease. After completion of study treatment, patients are followed monthly for 3 months,
every 3 months for 2 years, every 6 months for 3-5 years, and then annually thereafter or at
study termination.

PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.

Inclusion Criteria:

- Previously untreated, histologically confirmed mantle cell lymphoma.

- Measurable or evaluable disease.

- All stages are eligible.

- Age > 18 years.

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

- Adequate hepatic function:

- Bilirubin < 3 mg/dL.

- Transaminases (SGOT and/or SGPT) < than 2.5 times the upper limit of normal for
the institution, unless due to lymphomatous involvement.

- Serum creatinine < 1.5 mg/Dl.

- Ability to give informed consent.

- Women of childbearing potential must have a negative pregnancy test within 72 hours
of entering into the study. Males and females must agree to use adequate birth
control if conception is possible during the study. Women must avoid pregnancy and
men avoid fathering children while in the study.

- Life expectancy greater than 6 months.

Exclusion Criteria:

- Previous chemotherapy, immunotherapy or radiotherapy for this lymphoma

- Concurrent active malignancies, with the exception of in situ carcinoma of the cervix
and basal cell carcinoma of the skin.

- Grade 3 or 4 cardiac failure and/or ejection fraction < 50.

- Psychological, familial, sociological or geographical conditions that do not permit
treatment and/or medical follow-up required to comply with the study protocol.

- Patients with a known history of HIV or AIDS

- Presence of hepatitis or hepatitis B virus (HBV) infection

- Pregnant or breast-feeding women.

- Central nervous system (CNS) involvement