Chemotherapy and Rituximab With Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      OBJECTIVES:

        -  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.
    

Intervention name(s): filgrastim; rituximab; carmustine; cyclophosphamide; cytarabine; doxorubicin hydrochloride; etoposide; leucovorin calcium; methotrexate; prednisone; vincristine sulfate; peripheral blood stem cell transplantation
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure
Intervention description(s): 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; 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 5; 15 mg/kg IV infusion over 2 hours Day 6, Tx 4; 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 4; 2000 mg/sq m IV infusion BID over 2 hours x 8 doses Days 1-4, Tx 3; 50 mg/sq m IVP Day 3, Tx 1& 2; 40 mg/kg total dose continuous IV infusion over 96 hours Days 1-4, Tx 3; 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 & 2; 300 mg/sq m IV infusion over 4 hrs Day 2 Tx 1 & 2; 100 mg/sq m PO Days 3-7, Tx 1 & 2; 1.4 mg/sq m IVP Day 3, Tx 1 & 2; Stem cells collected during Tx 3 will be transfused follwing chemotx in Tx 4
Other intervention name(s): G-CSF; ara-C
Intervention MeSH terms: Leucovorin; Cytarabine; Prednisone; Cyclophosphamide; Carmustine; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Vincristine; Levoleucovorin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I mantle cell lymphoma; contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma