Combination Chemotherapy Plus Radiation Therapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
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. Combining chemotherapy with radiation therapy and peripheral stem
      cell transplantation may kill more tumor cells.

      PURPOSE: Phase II trial to study the effectiveness of high-dose combination chemotherapy plus
      radiation therapy followed by peripheral stem cell transplantation in patients with
      refractory or recurrent non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the efficacy of mobilization using filgrastim (G-CSF) with or without
           standard-dose ifosfamide, carboplatin, and etoposide (ICE), conditioning using
           ifosfamide and etoposide plus total body irradiation or high-dose ICE, and autologous
           peripheral blood stem cell (PBSC) transplantation as salvage therapy in patients with
           refractory, recurrent, or poor prognosis non-Hodgkin's lymphoma.

        -  Determine the efficacy of reinduction comprising ICE followed by autologous PBSC
           transplantation in these patients.

        -  Determine the ability of standard-dose ICE combined with hematopoietic growth factors to
           mobilize PBSC in these patients.

        -  Determine the contamination of PBSC by lymphoma cells in patients treated with this
           mobilization regimen.

        -  Determine the quality of life of patients treated with this regimen.

      OUTLINE: Patients are stratified according to disease status (relapsed vs refractory),
      lymphoma grade (low vs intermediate vs high), number of extranodal sites, serum lactic
      dehydrogenase, performance status, age, and volume of disease.

        -  Mobilization/harvest: Patients in first or greater complete remission (CR) are treated
           on regimen A, whereas patients with recurrent or refractory disease are treated on
           regimen B.

             -  Regimen A: Patients with poor prognosis intermediate-grade lymphoma (IGL) in first
                CR or IGL or low-grade lymphoma (LGL) in second or greater CR receive mobilization
                with filgrastim (G-CSF) subcutaneously (SC) daily on days 1-7. Autologous
                peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells on
                days 5 and 6 (and day 7 if needed).

             -  Regimen B: Patients who are currently on the MSKCC standard dose salvage therapy
                protocol with ifosfamide, carboplatin, and etoposide (ICE) for recurrent or
                refractory IGL receive additional mobilization with G-CSF after completion of the
                last course of ICE. Patients with recurrent or refractory IGL, immunoblastic
                lymphoma, or LGL who have not previously received ifosfamide and are not currently
                on the MSKCC standard dose salvage protocol with ICE receive ifosfamide IV and
                carboplatin on day 2 and etoposide IV on days 1-3 (standard-dose ICE) followed by
                G-CSF SC. When blood counts recover, autologous PBSC are harvested and selected for
                CD34+ cells.

             -  Regimens A and B: If additional hematopoietic growth factors (HGFs) become
                available, they may be administered concurrently with G-CSF. If inadequate CD34+
                cells are collected, then autologous bone marrow is harvested.

        -  Conditioning: Patients who are under age 60 and have not received dose-limiting
           radiotherapy are treated on regimen C. Patients who are age 60 and over and patients who
           are under age 60 and have received dose-limiting radiotherapy are treated on regimen D.

             -  Regimen C: Patients undergo hyperfractionated total body irradiation twice a day on
                days -10 to -7 and ifosfamide IV over 1 hour followed by etoposide IV over 23 hours
                on days -6 to -2.

             -  Regimen D: Patients receive ifosfamide IV over 1 hour, followed by etoposide IV
                over 11 hours, followed by carboplatin IV over 1 hour, followed by etoposide IV
                over 11 hours on days -7 to -3 (high-dose ICE).

             -  Regimens C and D: Patients with residual or relapsed disease may undergo boost
                radiotherapy twice a day, 5 days a week, for 1-2 weeks before conditioning or after
                transplantation.

        -  Transplantation: PBSC or bone marrow is reinfused on day 0. Patients receive G-CSF SC
           every 12 hours beginning on day 1 and continuing until blood counts recover. If
           additional HGFs become available, they may be administered concurrently with G-CSF.

      Quality of life is assessed at baseline and then at 6, 12, and 24 months after
      transplantation.

      Patients are followed at 1 and 3 months, every 3 months through year 2, every 4 months
      through year 5, and then every 6 months thereafter.

      PROJECTED ACCRUAL: A total of 80 patients (20 for regimen A and 60 for regimen B) will be
      accrued for this study.
    

Intervention name(s): filgrastim; sargramostim; carboplatin; etoposide; ifosfamide; autologous bone marrow transplantation; bone marrow ablation with stem cell support; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Procedure; Procedure; Procedure; Radiation
Intervention MeSH terms: Carboplatin; Etoposide; Ifosfamide; Sargramostim
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma