R-MACLO-IVAM and Thalidomide in Untreated Mantle Cell Lymphoma
RATIONALE: To evaluate the efficacy of a new high intensity chemotherapy regimen with thalidomide maintenance in patients with newly diagnosed mantle cell lymphoma
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:||Endpoint Classification: Efficacy Study
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 Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Percentage of participants achieving progression-free survival at 1, 3 and 5 years after the start of protocol therapy, based upon the International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL). Progression is defined as a ≥ 50% increase from nadir in the product of the two largest perpendicular diameters (PPD-size) of any previously identified abnormal node, or appearance of any new lesion.
- Overall Survival Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Percentage of participants who are alive up to five years after receipt of protocol therapy.
- Response Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Percentage of participants achieving complete response (CR) to protocol therapy according to International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL) using the CT imaging method. Patients were classified by best tumor response; CR was defined as normalization of the lactate dehydrogenase (LDH), complete disappearance of disease-related symptoms and lymph nodes, and clearance of lymphoma from involved organs; complete response unconfirmed (CRu) as a residual lymph node greater than 1.5 cm in greatest transverse diameter that had regressed by more than 75% or an indeterminate bone marrow examination; partial response (PR) as greater than 50% reduction in the involved lymph nodes, or disappearance of the involved lymph nodes but persistent bone marrow involvement; relapse/progression as new or increased lymph nodes, organomegaly, or reappearance of bone marrow involvement.
- Number of Patients Experiencing Adverse Events. [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Number of patients experiencing adverse events during the course of protocol therapy.
|Study Start Date:||April 2004|
|Study Completion Date:||July 2015|
|Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Rituximab, Methotrexate, Doxorubicin, Cyclophosphamide and Vincristine (cycle 1), followed by Rituximab, Ifosfamide (and Mesna), Etoposide and Cytarabine (cycle 2). These two cycles are repeated once, and patients achieving complete repose receive maintenance Thalidomide.
Rituximab 375 mg/m2 IV, Days 1 of all 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 once a day (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 5 percent dextrose in water (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 1 and 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 subcutaneous (SQ) starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4)
Other Name: NeupogenDrug: Granisetron
Granisetron 1 mg IV on Day 1, Cycle 1 and 3
Other Names:Drug: Decadron
Decadron 10 mg IV on Day 1, Cycles 1 and 3
- 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.
- 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.
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|