Combination Chemotherapy in Treating Children 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. Combining more than one drug may kill more cancer cells.

      PURPOSE: Phase III trial to study the effectiveness of combination chemotherapy in treating
      children who have non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Assess the event free survival at 2 and 5 years of children with T cell or pre-B cell
           non-Hodgkin's lymphoma treated with a sequential induction regimen, a consolidation
           regimen, a reintensification regimen, and a maintenance regimen.

        -  Assess the rate of local relapse at 2 and 5 years of these children after receiving this
           treatment.

        -  Determine the toxicity of this treatment in these patients.

        -  Determine the overall survival of these children at 5 years after receiving this
           treatment.

      OUTLINE: This is a multicenter study.

      Patients receive 5 weeks of induction chemotherapy consisting of prednisone IV twice a day on
      days 1-28, then decreasing in dose on days 29-35; vincristine IV on days 8, 15, 22, and 29;
      cyclophosphamide IV over 1 hour on day 8; daunorubicin IV over 24 hours on days 15, 22, and
      29; asparaginase IV or IM on days 16, 18, 20, 23, 25, 27, 30, and 32; and methotrexate IV
      over 3 hours on day 8. Patients also receive methotrexate and methylprednisolone
      intrathecally (IT) on days 1, 4, 9, and 15.

      Patients with a response over 50% proceed to 4-8 weeks of consolidation therapy. This regimen
      consists of vincristine IV on day 15, cyclophosphamide IV over 1 hour followed by
      methotrexate over 3 hours on day 1, cytarabine IV on days 2-5 and 8-11, asparaginase IV or IM
      on days 16 and 23, and methotrexate IV over 3 hours on day 15. Patients also receive
      methotrexate and methylprednisolone IT on days 2 and 16. Patients who achieve complete
      remission after 4 weeks repeat consolidation therapy for another course.

      Patients then receive 4 weeks of interphase therapy consisting of oral mercaptopurine on days
      1 and 22, methotrexate IV over 3 hours on days 1 and 15, and methotrexate and
      methylprednisolone IT on days 2 and 16.

      Patients with pre-B cell lymphoma then proceed to maintenance therapy. Patients with T cell
      lymphoma proceed to reinduction therapy. Reinduction A is a 4 week course of chemotherapy
      administered during months 1, 3, and 5 and consists of vincristine IV on day 1; methotrexate
      IV over 3 hours on days 1, 8, 15, and 22; methotrexate and methylprednisolone IT on day 2;
      asparaginase IM or IV on day 2; and oral mercaptopurine. Reinduction B is also a 4 week
      course of therapy administered during months 2, 4, and 6. This consists of oral prednisone
      twice a day on days 1-5; cytarabine subcutaneously twice a day on days 1-4; methotrexate IV
      on days 1, 8, 15, and 22; and oral mercaptopurine.

      Patients then proceed to maintenance therapy, which consists of methotrexate and
      mercaptopurine once a week. Patients with stage I, II, or III disease continue maintenance
      therapy for 18 months, while patients with stage IV disease continue this therapy for 24
      months.

      Patients with stage IV disease with neuromeningeal involvement receive triple intrathecal
      therapy consisting of methotrexate, cytarabine, and methylprednisolone, then reinduction A
      for months 1, 2, and 3, then reinduction B for months 4, 5, and 6 (if T cell lymphoma). These
      patients also receive cerebral irradiation during months 4 and 5. Patients with pre-B cell
      disease receive cerebral irradiation after intensification therapy.

      Patients with less than 50% response after induction therapy or incomplete remission after
      4-8 weeks of consolidation therapy, or who have a recurrence of disease are treated with the
      "VANDA" regimen consisting of dexamethasone on days 1-5; cytarabine over 3 hours twice a day
      on days 1 and 2; mitoxantrone IV over 1 hour on days 3 and 4; etoposide IV over 1 hour on
      days 3-5; and asparaginase IV over 1 hour or IM on days 7, 9, 11, and 13. Patients also
      receive triple intrathecal therapy (methotrexate, cytarabine, and methylprednisolone) on day
      5.

      Patients are followed every 2 months for 1 year, every 3 months for 2 years, every 4 months
      for 1 year, every 6 months for 1 year, then annually thereafter.

      PROJECTED ACCRUAL: A total of 200 patients will be accrued for this study within 4 years.
    

Intervention name(s): asparaginase; cyclophosphamide; cytarabine; daunorubicin hydrochloride; dexamethasone; etoposide; mercaptopurine; methotrexate; methylprednisolone; mitoxantrone hydrochloride; prednisone; vincristine sulfate; radiation therapy
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Radiation
Intervention MeSH terms: Cytarabine; Dexamethasone; Prednisone; Methylprednisolone; Cyclophosphamide; Methotrexate; Etoposide; Vincristine; Daunorubicin; Asparaginase; Mitoxantrone; Mercaptopurine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I childhood lymphoblastic lymphoma; stage II childhood lymphoblastic lymphoma; stage III childhood lymphoblastic lymphoma; stage IV childhood lymphoblastic lymphoma