Chemotherapy and Rituximab With or Without Total-Body Irradiation and Peripheral Stem Cell Transplant in Treating Patients With Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells
      and either kill them or deliver cancer-killing substances to them without harming normal
      cells. Combining chemotherapy with monoclonal antibody therapy, total-body irradiation, and
      peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy
      drugs and kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving chemotherapy with rituximab followed
      by combination chemotherapy with or without rituximab, total-body irradiation, and peripheral
      stem cell transplant works in treating patients with lymphoma.
    

Detailed description: 
      OUTLINE: Patients are stratified according to risk (low-intermediate vs high-intermediate or
      high).

      Patients receive induction chemotherapy comprising cyclophosphamide IV, doxorubicin IV over
      15 minutes, and vincristine IV over 1-2 minutes on day 1; oral prednisone once daily on days
      1-5; and filgrastim (G-CSF) subcutaneously (SC) once daily on days 7-11 or PEG-filgrastim
      once at least 24 hours after infusion. Patients also receive rituximab IV 2-3 days apart for
      a total of 2 doses during the week prior to the first course of chemotherapy and on day 1 of
      courses 2-4 of chemotherapy. Treatment repeats every 14 days for a total of 4 courses in the
      absence of disease progression or unacceptable toxicity.

      After the completion of induction chemotherapy, patients undergo CT scan and positron
      emission tomography (PET) scanning. If the PET scan is positive in one or more nodal sites, a
      repeat biopsy is performed. Patients with a negative PET scan OR a negative repeat biopsy
      (including no evidence of lymphoma on repeat bone marrow biopsy) are assigned to receive
      regimen A for consolidation therapy. Patients with a positive repeat biopsy are assigned to
      receive regimen B for consolidation therapy.

        -  Regimen A: Patients receive consolidation chemotherapy comprising etoposide IV over 1
           hour on days 1-3, ifosfamide IV continuously over 24 hours on day 2, carboplatin IV on
           day 2, and G-CSF SC once daily on days 5-12 or PEG-filgrastim once at least 24 hours
           after infusion. Treatment repeats every 14 days for a total of 3 courses in the absence
           of disease progression or unacceptable toxicity.

        -  Regimen B: Patients receive consolidation chemotherapy as in regimen A for 3 courses.
           Patients also receive rituximab IV on days -3 to -1 of course 3 of chemotherapy.
           Patients undergo leukapheresis at the completion of course 3 (G-CSF continues from day 5
           until the end of leukapheresis). After completion of leukapheresis, patients begin a
           regimen of high-dose chemoradiotherapy comprising either total body irradiation twice
           daily on days -10 to -7 and ifosfamide IV over 1 hour and etoposide IV continuously on
           days -6 to -2 or BEAM chemotherapy comprising carmustine, etoposide, cytarabine, and
           melphalan. Autologous peripheral blood stem cells (APBSC) are reinfused on day 0.
           Patients also receive G-CSF SC daily beginning on day 5 and continuing until blood
           counts recover. Beginning on day 42 post-APBSC, if blood counts have recovered, patients
           receive rituximab IV once weekly for 4 weeks. Rituximab is repeated beginning on day 180
           in the absence of disease progression.

      Patients who receive consolidation therapy on regimen A are followed at 4-6 weeks after
      chemotherapy and patients who receive consolidation therapy on regimen B are followed at
      90-120 days after transplantation. All patients are followed closely for 5 years and then
      annually thereafter.

      PROJECTED ACCRUAL: A total of 40-98 patients will be accrued for this study within 4 years.
    

Intervention name(s): filgrastim; rituximab; carboplatin; cyclophosphamide; doxorubicin hydrochloride; etoposide; ifosfamide; prednisone; vincristine sulfate; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention MeSH terms: Prednisone; Cyclophosphamide; Ifosfamide; Rituximab; Carboplatin; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma