Combination Chemotherapy Followed By Radiation Therapy in Treating Patients With 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 cancer cells from dividing
      so they stop growing or die. Combining more than one drug and giving the drugs in different
      ways may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer
      cells. It is not yet known which combination chemotherapy regimen followed by radiation
      therapy is more effective in treating aggressive non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens
      followed by radiation therapy to compare how well they work in treating patients with
      aggressive non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the efficacy of standard-dose vs high-dose cyclophosphamide, doxorubicin,
           vincristine, etoposide, and prednisone followed by radiotherapy, in terms of time to
           treatment failure, in patients with aggressive non-Hodgkin's lymphoma.

        -  Compare the acute and long-term toxic effects of these regimens in these patients.

        -  Compare the complete response rate, survival and tumor control, and disease-free
           survival in patients treated with these regimens.

        -  Analyze the time to relapse after radiotherapy in these patients.

      OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
      according to LDH levels (no greater than upper limit of normal [ULN] vs greater than ULN),
      initial bulky disease (yes vs no), stage (I or II vs II or IV), ECOG performance status (0 or
      1 vs 2 or 3), and participating center. Patients are randomized to 1 of 2 treatment arms as
      follows:

        -  Arm I (Standard dose): Patients receive cyclophosphamide IV, doxorubicin IV, and
           vincristine IV on day 1; etoposide IV on days 1-3; and oral prednisone on days 1-5
           (CHOEP) in standard doses.

        -  Arm II (Escalated dose): Patients receive high-dose CHOEP as in arm I. Patients also
           receive filgrastim (G-CSF) subcutaneously on days 6-12.

      In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease
      progression or unacceptable toxicity.

      After completion of CHOEP chemotherapy, patients with initial bulky disease or extranodal
      involvement undergo radiotherapy 5 days a week for 4 weeks.

      Patients who undergo radiotherapy are followed at 2 months after radiotherapy. All patients
      (including those who undergo radiotherapy) are followed every 3 months for 2 years and then
      every 6 months for 3 years.

      PROJECTED ACCRUAL: A total of 389 patients were accrued for this study.
    

Intervention name(s): filgrastim; EPOCH regimen; cyclophosphamide; doxorubicin hydrochloride; etoposide; prednisone; vincristine sulfate; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Drug; Radiation
Intervention MeSH terms: Prednisone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: contiguous stage II grade 3 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; stage I grade 3 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 3 follicular lymphoma; contiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; stage I adult diffuse mixed cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse mixed cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; contiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult Burkitt lymphoma; stage I adult diffuse large cell lymphoma; stage I adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage III adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult Burkitt lymphoma; contiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; stage I adult immunoblastic large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; contiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; stage I adult lymphoblastic lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; stage I mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma