Chemotherapy and Rituximab With Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.
PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy and rituximab with peripheral stem cell transplantation in treating patients who have mantle cell lymphoma.
Drug: doxorubicin hydrochloride
Drug: leucovorin calcium
Drug: vincristine sulfate
Procedure: peripheral blood stem cell transplantation
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study Of Intensive Induction Chemotherapy Followed By Autologous Stem Cell Transplantation Plus Immunotherapy For Mantle Cell Lymphoma|
- Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]Disease free and overall survival
|Study Start Date:||June 2001|
|Study Completion Date:||September 2009|
|Primary Completion Date:||December 2006 (Final data collection date for primary outcome measure)|
Experimental: Chemo/immuno/autolog transplant
Intensive chemotherapy followed by autologous stem cell transplant and immunotherapy for mantle cell lymphoma
5 ug/kg subQ daily day 4 until ANC >10,000 (or ANC> 5000 2X)Tx 1, 2, 4 10 ug/kg subQ daily day 14 until completion of PBSC collection Tx 3
Other Name: G-CSFBiological: rituximab
375 mg/sq m IV infusion at , or = 400 mg/hr day 1 Tx 1, 2, days 5 & 12 Tx 3, and weekly for 2 doses Tx 5Drug: carmustine
15 mg/kg IV infusion over 2 hours Day 6, Tx 4Drug: cyclophosphamide
2000 mg/sq m IV infusion over 2 hours Day 3, Tx 1 & 2 100 mg/kg IV infusion over 2 hours Day 2, Tx 4Drug: cytarabine
2000 mg/sq m IV infusion BID over 2 hours x 8 doses Days 1-4, Tx 3
Other Name: ara-CDrug: doxorubicin hydrochloride
50 mg/sq m IVP Day 3, Tx 1& 2Drug: etoposide
40 mg/kg total dose continuous IV infusion over 96 hours Days 1-4, Tx 3Drug: leucovorin calcium
50 mg/sq m IV infusion q 6 hours x 3 doses after MTX, then 10 mg/sq m IV/PO q 6 hrs until MTX levels <0.05 uM, Tx 1 & 2Drug: methotrexate
300 mg/sq m IV infusion over 4 hrs Day 2 Tx 1 & 2Drug: prednisone
100 mg/sq m PO Days 3-7, Tx 1 & 2Drug: vincristine sulfate
1.4 mg/sq m IVP Day 3, Tx 1 & 2Procedure: peripheral blood stem cell transplantation
Stem cells collected during Tx 3 will be transfused follwing chemotx in Tx 4
- Determine the two-year progression-free survival of patients with mantle cell lymphoma treated with intensive chemotherapy and rituximab with autologous peripheral blood stem cell (PBSC) transplantation.
- Determine the complete and partial response rates of patients treated with this regimen.
- Determine the disease-free and overall survival of patients treated with this regimen.
- Determine the autologous immune reconstitution in patients treated with this regimen.
- Determine the feasibility of this regimen in this patient population.
- Determine whether treatment with rituximab during autologous PBSC transplantation reduces the amount of contaminating lymphoma in the autologous PBSC product.
OUTLINE: This is a multicenter study.
Patients receive induction therapy comprising rituximab IV over 4-6 hours on day 1; methotrexate IV over 4 hours on day 2; cyclophosphamide IV over 2 hours, doxorubicin IV, and vincristine IV on day 3; and oral prednisone on days 3-7. Patients also receive leucovorin calcium IV every 6 hours beginning on day 3 and continuing until blood levels of methotrexate are safe. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.
Induction therapy repeats every 21-28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Rituximab may be omitted during course 1 if circulating mantle cells are excessive. Patients may receive a third course if more than 15% persistent bone marrow involvement is documented.
Patients with stable or responding disease begin consolidation therapy 29 days after the start of the final course of induction therapy. Patients receive cytarabine IV over 2 hours twice daily and etoposide IV over 96 hours on days 1-4. Patients also receive rituximab IV over 4-6 hours on days 5 or 6 and 12 or 13 and G-CSF SC beginning on day 14 and continuing until leukapheresis is complete. Patients undergo leukapheresis beginning between days 22-25 and continuing until adequate CD34 cells are collected.
Beginning 4 weeks after recovery from consolidation therapy, patients receive high-dose therapy comprising carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous peripheral blood stem cell (PBSC) transplantation on day 0. Patients receive G-CSF SC beginning on day 6 and continuing until blood counts recover.
After blood counts recover and more than 35 days after autologous PBSC transplantation, patients receive rituximab IV over 4-6 hours weekly for 2 weeks.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for up to 10 years.
PROJECTED ACCRUAL: At least 45 patients will be accrued for this study within 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00020943
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|Study Chair:||Lloyd Damon, MD||University of California, San Francisco|