Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Aggressive Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining peripheral stem cell transplantation with more than one
      drug regimen may kill more tumor cells. It is not known whether receiving standard
      combination chemotherapy alone is more effective than receiving multiple combination
      chemotherapy plus peripheral stem cell transplantation for aggressive non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is comparing giving different combination
      chemotherapy regimens together with peripheral stem cell transplantation to see how well they
      work in treating patients with newly diagnosed aggressive non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the efficacy of sequential high-dose chemotherapy and autologous peripheral
           blood stem cell transplantation with standard chemotherapy (cyclophosphamide,
           doxorubicin, vincristine, and prednisone) in patients with newly diagnosed aggressive
           non-Hodgkin's lymphoma and poor prognostic factors.

        -  Compare the toxic effects of these 2 regimens in these patients.

        -  Compare the response rates and overall survival of patients treated with these regimens.

      OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two
      treatment arms.

        -  Arm I: Patients receive standard chemotherapy comprising cyclophosphamide, doxorubicin,
           vincristine, and prednisone (CHOP). Patients receive cyclophosphamide IV over 30
           minutes, doxorubicin IV, and vincristine IV on day 1. Patients receive oral prednisone
           daily on days 1-5. Treatment repeats every 21 days for 6-8 courses. Patients with bulky
           disease at diagnosis or residual disease after chemotherapy receive radiotherapy 30-60
           days after initiation of the last course of CHOP.

        -  Arm II: Patients receive 5 regimens of chemotherapy administered in sequence.

             -  Regimen A : Patients receive CHOP as in Arm I.

             -  Regimen B: Three weeks after starting regimen A, patients receive high-dose
                cyclophosphamide IV over 24 hours on day 1. Patients without initial bone marrow
                involvement receive filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 3
                and continuing until autologous peripheral blood stem cells (PBSC) are harvested.
                PBSC are harvested on days 13-15 or when blood counts recover. Patients with
                initial bone marrow involvement do not undergo harvest of PBSC at this time, but
                receive G-CSF SC daily.

             -  Regimen C: Two to three weeks after high-dose cyclophosphamide, patients receive
                vincristine IV and high-dose methotrexate IV over 6 hours on day 2. Patients
                receive leucovorin calcium IV every 6 hours on days 3-5 beginning 24 hours after
                initiation of the methotrexate infusion.

             -  Regimen D: Within 1-2 weeks after the administration of methotrexate in regimen C,
                patients receive methylprednisolone IV followed 6 hours later by high-dose
                etoposide IV over 10 hours on day 1. Patients receive methylprednisolone IV on day
                2. Patients without initial bone marrow involvement receive G-CSF SC daily
                beginning on day 3 and continuing until blood counts recover. Patients with initial
                bone marrow involvement receive G-CSF SC daily until autologous PBSC are harvested.
                PBSC are harvested on days 10-14 or when blood counts recover.

             -  Regimen E: Myeloablative therapy and autologous PBSC transplantation begin 16-40
                days after the administration of etoposide. Patients receive mitoxantrone IV over 1
                hour every 2 hours for 3 doses on day 2 and melphalan IV over 30 minutes on day 5.
                PBSC are reinfused on day 6 beginning at least 24 hours after the administration of
                melphalan. Patients receive G-CSF SC or by continuous infusion beginning on day 7.

      Patients with bulky disease at diagnosis or residual disease after chemotherapy receive
      radiotherapy 30-100 days after PBSC transplantation.

      Patients at high risk of developing CNS disease receive prophylactic intrathecal
      chemotherapy. Patients may receive cytarabine, methotrexate, and hydrocortisone or
      methotrexate and hydrocortisone every 1-2 weeks for 6 courses.

      Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
      annually thereafter.

      PROJECTED ACCRUAL: Approximately 400 patients will be accrued for this study within 4-5
      years.
    

Intervention name(s): filgrastim; CHOP regimen; cyclophosphamide; cytarabine; doxorubicin hydrochloride; etoposide; leucovorin calcium; melphalan; methotrexate; methylprednisolone; mitoxantrone hydrochloride; prednisone; therapeutic hydrocortisone; vincristine sulfate; bone marrow ablation with stem cell support; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention MeSH terms: Leucovorin; Cytarabine; Prednisone; Methylprednisolone; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cyclophosphamide; Melphalan; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Vincristine; Mitoxantrone; Levoleucovorin
Allocation: Randomized
Primary purpose: Treatment
Keywords: stage I adult diffuse mixed cell lymphoma; stage I adult diffuse large cell lymphoma; stage I adult immunoblastic large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; contiguous stage II adult diffuse mixed cell lymphoma; contiguous stage II adult immunoblastic large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; anaplastic large cell lymphoma