Chemotherapy and Peripheral Stem Cell Transplant With or Without Monoclonal Antibody Therapy 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 work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. Peripheral stem cell
      transplant may be able to replace immune cells that were destroyed by the chemotherapy.
      Monoclonal antibodies, such as rituximab, can block tumor growth in different ways. Some
      block the ability of tumor cells to grow and spread. Others find tumor cells and help kill
      them or carry tumor-killing substances to them. It is not yet known if giving more than one
      drug (combination chemotherapy) plus peripheral stem cell transplant is more effective with
      or without monoclonal antibody therapy in treating non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is studying how well chemotherapy plus peripheral
      stem cell transplant with or without monoclonal antibody therapy works in treating patients
      with relapsed non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the partial and complete response rates in patients with relapsed, CD20
           positive, aggressive B-cell non-Hodgkin's lymphoma treated with dexamethasone,
           cisplatin, and cytarabine in combination with etoposide, ifosfamide, and methotrexate
           with or without rituximab followed by carmustine, etoposide, cytarabine, melphalan, and
           autologous peripheral blood stem cell transplantation (APBSCT).

        -  Compare the effect of APBSCT with or without rituximab on the overall and event-free
           survival of these patients.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
      participating center. Patients are randomized to one of two treatment arms.

        -  Arm I: Patients receive DHAP induction chemotherapy comprising dexamethasone orally or
           IV on days 1-4, cisplatin IV continuously over 24 hours on day 1, and cytarabine IV over
           3 hours every 12 hours on day 2. Beginning 3-4 weeks after DHAP, patients receive VIM
           induction chemotherapy comprising etoposide IV over 2 hours on days 1, 3, and 5;
           ifosfamide IV over 1 hour on days 1-5; and methotrexate IV on days 1 and 5. Beginning
           3-4 weeks after VIM, patients with partial or complete response after DHAP and VIM
           receive a second course of DHAP (patients with progressive or unresponsive disease after
           DHAP but responsive disease after VIM receive a second course of VIM) followed by
           filgrastim (G-CSF) subcutaneously beginning on day 10 and continuing until a target
           number of cells are collected.

        -  Arm II: Patients receive induction chemotherapy and G-CSF as in arm I. At 1 day after
           the last dose of each chemotherapy course, patients also receive rituximab IV once for a
           maximum of 3 courses.

      At 4-5 weeks after the completion of the last induction chemotherapy course, responsive
      patients in both arms receive BEAM conditioning chemotherapy comprising carmustine IV over 60
      minutes on day -6, etoposide IV over 60 minutes and cytarabine IV over 30 minutes on days -5
      to -2, and melphalan IV over 15 minutes on day -1. Patients undergo autologous peripheral
      blood stem cell transplantation on day 0. After transplantation, patients in partial
      remission may undergo radiotherapy to nodal sites with residual tumor mass.

      Patients are followed every 6 months for 3 years and then annually thereafter.

      PROJECTED ACCRUAL: A total of 296-340 patients (148-170 per treatment arm) will be accrued
      for this study within 4-5 years.
    

Intervention name(s): filgrastim; rituximab; carmustine; cisplatin; cytarabine; dexamethasone; etoposide; ifosfamide; melphalan; methotrexate; bone marrow ablation with stem cell support; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention MeSH terms: Cytarabine; Dexamethasone; Rituximab; Methotrexate; Etoposide; Melphalan; Ifosfamide; Carmustine
Allocation: Randomized
Primary purpose: Treatment
Keywords: recurrent grade 3 follicular lymphoma; recurrent adult diffuse large cell lymphoma