SWOG-9704 Chemoradiotherapy and Peripheral Stem Cell Transplantation Compared With Combination Chemotherapy in Treating Patients With 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. Radiation therapy uses high-energy x-rays to damage cancer
      cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of
      chemotherapy and radiation and kill more cancer cells. It is not yet known whether
      chemoradiotherapy plus peripheral stem cell transplantation is more effective than
      combination chemotherapy alone in treating non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is studying chemoradiotherapy and peripheral stem
      cell transplantation to see how well they work compared to combination chemotherapy in
      treating patients with stage II, stage III, or stage IV non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the overall survival and progression-free survival of patients with
           intermediate- or high-grade non-Hodgkin's lymphoma treated with high-dose
           chemoradiotherapy and autologous peripheral blood stem cell transplantation (APBSCT) vs
           conventional dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (or
           CHOP plus rituximab for CD20+ disease) with possible late APBSCT.

        -  Compare the toxic effects of these regimens in this patient population.

      OUTLINE: This is a randomized study. Patients are stratified according to disease risk
      (intermediate-high vs high).

      Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes,
      doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients with
      CD20-positive disease also receive rituximab IV on day 1 (or day 0 during course 1 only).
      Treatment repeats every 3 weeks for 5 courses in the absence of disease progression or
      unacceptable toxicity.

      Within 35 days of completing the fifth course, patients with partial or complete response are
      randomized to one of two treatment arms.

        -  Arm I: Patients receive CHOP (or CHOP plus rituximab [CHOP-R]) as above. Treatment
           repeats every 3 weeks for 3 additional courses. After completion of chemotherapy,
           patients are encouraged to undergo harvest of peripheral blood stem cells (PBSC) for
           possible use at time of relapse. After completion of 8 courses, patients receive no
           additional therapy until disease progression or biopsy-proven disease.

        -  Arm II: Patients receive one additional course of CHOP/CHOP-R followed by filgrastim
           (G-CSF), sargramostim (GM-CSF), or other colony-stimulating factors used singly or in
           combination according to center preference. PBSC are harvested and selected for CD34+
           cells. Patients under age 61 receive one of two preparative regimens: a total body
           irradiation (TBI)-based regimen comprising irradiation administered twice daily on days
           -8 to -5, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 1 hour on
           day -2 OR carmustine IV over 2 hours on days -6 to -4 and etoposide and cyclophosphamide
           as in the TBI-based regimen. Patients age 61 to 65 receive the augmented regimen
           comprising carmustine, etoposide, and cyclophosphamide as above. Patients receive
           involved field radiotherapy prior to the preparative regimen only if there is
           biopsy-proven residual bulk disease and at the discretion of the center. PBSC are
           reinfused 36-48 hours after completion of cyclophosphamide. If both bone marrow and PBSC
           are harvested, bone marrow is reinfused on day 0 and then PBSC are reinfused either the
           same day or the following day.

      Patients are followed every 6 months for 2 years and then annually thereafter.

      PROJECTED ACCRUAL: Approximately 360 patients (at least 135 per treatment arm) will be
      accrued for this study within 5 years.
    

Intervention name(s): rituximab; CHOP regimen; carmustine; cyclophosphamide; doxorubicin hydrochloride; etoposide; prednisone; 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; Procedure; Procedure; Radiation
Intervention description(s): 375 mg/m2 IV every 21 days
Intervention MeSH terms: Prednisone; Cyclophosphamide; Carmustine; Rituximab; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage III grade 3 follicular lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult Burkitt lymphoma; stage IV grade 3 follicular lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult Burkitt lymphoma; contiguous stage II grade 3 follicular lymphoma; contiguous stage II adult diffuse small cleaved 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; contiguous stage II adult Burkitt lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II adult diffuse small cleaved 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; noncontiguous stage II adult Burkitt lymphoma