Rituximab and Combination Chemotherapy Followed By Thalidomide in Treating Patients With Previously Untreated Mantle Cell Lymphoma
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as thalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with combination chemotherapy and thalidomide may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy followed by thalidomide works in treating patients with previously untreated mantle cell lymphoma.
Drug: Filgrastim (G-CSF)
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (Maclo/Ivam) in Patients With Previously Untreated Mantle Cell Lymphoma|
- Progression-free survival at 6, 12, 18, and 24 months [ Time Frame: 6, 12, 18, and 24 months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2004|
|Estimated Study Completion Date:||April 2014|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
|Experimental: MACLO IVAM||
Rituximab 375 mg/m2 IV, Days 1, 4 Cycles
Other Name: RituxanDrug: Cyclophosphamide
Cyclophosphamide 800 mg/m2 IV, Day 1, Cyclophosphamide 200 mg/m2 IV Days 2 - 5, Cycles 1 and 3. Cyclophosphamide will be given in 100 cc NS IV over 30 minutes.
Other Name: CytoxanDrug: Cytarabine
Cytarabine 2 grams/m2 IV every 12 hours x 4 doses, Days 1 and 2, Cycles 2 and 4.
Other Name: AraCDrug: Doxorubicin
Doxorubicin 45 mg/m2 IV bolus, DAy 1, Cycles 1 and 3
Other Name: AdriamycinDrug: Etoposide
Etoposide 60 mg/m2 IV daily x 5 days, Cycles 2 and 4
Other Name: VP16Drug: Ifosfamide
Ifosfamide 1.5 grams/m2 IV QD x 5 days, Cycles 2 and 4
Other Name: IfexDrug: Leucovorin
Leucovorin 180 mg/m2 IV beginning 36 hours after start of methotrexate infusion and then 12 mg/m2 IV every 6 hours until methotrexate level is below 0.01 nM. Day 10, Cycles 1 and 3.
Other Name: Folinic AcidDrug: Methotrexate
Methotrexate 1,200 mg/m2 in 250 cc D5W IV over 1 hour followed by Methotrexate 5,520 mg/m2 in 1,000 cc D5W by continuous infusion over 23 hours (240 mg/m2 every hour for 23 hours). Day 10, Cycles 1 and 3.
Other Name: amethopterinDrug: Thalidomide
Other Name: ThalomidDrug: Vincristine
Vincristine 1.5 mg/m2 IVP (maximum of 2 mg), Day 8 , Cycles 1 and 3.
Other Name: OncovinDrug: Mesna
Mesna 360 mg/m2 IV every 3 hours x 5 days, Cycles 2 and 4
Other Name: MesnexDrug: Filgrastim (G-CSF)
G-CSF 480 mcg SQ starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4)
Other Name: Neupogen
- Determine the progression-free survival of patients with previously untreated mantle cell lymphoma treated with rituximab and combination chemotherapy comprising vincristine, doxorubicin hydrochloride, cyclophosphamide, methotrexate, ifosfamide, cytarabine, and etoposide followed by thalidomide.
- 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: Patients receive rituximab IV and doxorubicin hydrochloride IV over 3-5 minutes on day 1, vincristine IV on days 1 and 8, cyclophosphamide IV over 30 minutes on days 1-5, methotrexate IV over 24 hours on day 10, and leucovorin calcium IV every 6 hours beginning on day 11 and continuing until the level of methotrexate in the blood is within a safe range. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 13 and continuing until blood counts recover. When absolute neutrophil count (ANC) reaches 1,500/mm^3, patients receive rituximab IV on day 1 (i.e., the day ANC reaches 1,500/mm^3), ifosfamide IV over 1 hour on days 1-5, cytarabine IV over 3 hours every 12 hours on days 1 and 2, and etoposide IV over 1 hour on days 1-5. Patients also receive G-CSF SC once daily beginning on day 7 and continuing until blood counts recover. Approximately 2-3 weeks later, patients receive another course of therapy as above.
Patients in complete remission after 2 courses of rituximab and combination chemotherapy receive oral thalidomide daily. Treatment with thalidomide continues for 1 year in the absence of disease progression or unacceptable toxicity.
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.
PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00450801
|United States, Florida|
|University of Miami Sylvester Comprehensive Cancer Center - Miami|
|Miami, Florida, United States, 33136|
|Study Chair:||Izidore S. Lossos, MD||University of Miami Sylvester Comprehensive Cancer Center|