Combination Chemotherapy in Treating Patients With Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
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 chemotherapy with peripheral stem cell transplantation
      may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

      PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of
      combination chemotherapy in treating patients who have intermediate-grade or immunoblastic
      lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the efficacy of early intensification vs alternating triple chemotherapy in
           patients with intermediate-grade or immunoblastic lymphoma with poor prognostic
           features.

        -  Compare, in a prospective manner, the cost/benefit ratio of these regimens in these
           patients.

        -  Determine the value of monitoring minimal residual disease detection via in vitro
           culture methods and polymerase chain reaction analysis of peripheral stem cell apheresis
           products and by longitudinal monitoring of blood and bone marrow samples in these
           patients treated with these regimens.

      OUTLINE: This is a randomized study. Patients are stratified according to tumor score (3 or 4
      vs 5 or 6).

      During the first course of induction, patients receive IDSHAP comprising idarubicin (IDA) and
      cisplatin IV continuously on days 1-4, cytarabine (ARA-C) IV over 2 hours on day 5, and
      methylprednisolone (MePRDL) IV over 15 minutes on days 1-5. During the second course of
      induction, patients receive MBIDCOS comprising vincristine, bleomycin, and cyclophosphamide
      IV over 15 minutes on day 1, IDA IV continuously and MePRDL IV over 15 minutes on days 1-3,
      methotrexate (MTX) IV over 2 hours on day 10, and oral leucovorin calcium every 6 hours on
      days 11 and 12. Each course lasts 3 weeks in the absence of disease progression or
      unacceptable toxicity.

      Patients with stable or responding disease after induction are randomized to 1 of 2 treatment
      arms.

      Arm I

        -  Patients receive the following 3 courses of early intensification.

             -  First course: Patients receive ifosfamide (IFF) IV continuously and etoposide
                (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) is
                administered subcutaneously (SC) beginning on day 5 and continuing until blood
                counts recover and then autologous peripheral blood stem cells (PBSC) are
                harvested, selected for CD34 positive cells, and purged in vitro. If more than 5%
                of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16
                are administered before PBSC harvest.

             -  Second course: Patients receive IFF IV continuously on days 1-3, mitoxantrone
                (DHAD) IV on day 1, and G-CSF SC as in the first course.

             -  Third course: Patients receive carmustine IV over 1 hour on day -6, ARA-C and VP-16
                IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused
                on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood
                counts recover. Each course lasts 3 weeks in the absence of disease progression or
                unacceptable toxicity.

      Arm II

        -  Patients receive IDSHAP during courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF
           and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses
           1, 4, and 7. Each course lasts 4 weeks in the absence of disease progression or
           unacceptable toxicity.

      Patients with residual disease after completion of arm I or II treatment undergo radiotherapy
      to areas of bulk disease if feasible. Patients on both arms with meningeal involvement
      receive ARA-C intrathecally (IT) alternated with MTX every other day until 1 week after
      clearing of CNS disease and then 2 IT injections during every course of chemotherapy
      thereafter. Patients with divergent histology who achieve complete response after completion
      of arm I or II treatment receive interferon alfa 3 times a week for 1 year.

      Patients are followed at 1 month, every 3 months for 1 year, every 6 months for 1 year, and
      then annually for 2 years.

      PROJECTED ACCRUAL: A maximum of 136 patients will be accrued for this study within 4 years.
    

Intervention name(s): Bleomycin Sulfate (BLM); Filgrastim (G-CSF); Recombinant Interferon Alfa; Carmustine; Cisplatin (CDDP); Cyclophosphamide; Cytarabine (ARA-C); Etoposide (VP-16); Idarubicin; Ifosfamide; Leucovorin Calcium; Melphalan; Methotrexate; Methylprednisolone; mitoxantrone hydrochloride (DHAD); Vincristine Sulfate; Peripheral Blood Stem Cell Transplantation; Radiation Therapy
Intervention type(s): Biological; Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention description(s): Arm 1: Administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover through Course 1 then 2 courses administered before PBSC harvest and same regimen with Course 2, then daily with Day 0 of infusion.; Arm 1, Course 3, IV over 1 hour on day -6.; Arm 1, Course 3, every 12 hours on days -5 to -2.; Course 1, IV over 2 hours every 12 hours on days 1-3; Course 3, every 12 hours on days -5 to -2.; During Course 1, IV continuously; Course 2, IV continuously on days 1-3.; Arm 1, Course 2, IV on day 1.; Infusion of stem cells on Day 0.
Other intervention name(s): Blenoxane; BLM; G-CSF; Neupogen; BiCNU; BiCNUI; Platinol; Platinol-AQ; Cytoxan; Neosar; ARA-C; Cytosar; DepotCyt; Cytosine arabinosine hydrochloride; VePesid; Idamycin; Ifex; Leucovorin; Citrovorum; Wellcovorin; Alkeran; Depo-Medrol; Medrol; Solu-Medrol; mitoxantrone; Novantrone; autologous peripheral blood stem cells; PBSC; RT
Intervention MeSH terms: Leucovorin; Interferons; Cytarabine; Interferon-alpha; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Melphalan; Ifosfamide; Carmustine; Cisplatin; Methotrexate; Etoposide; Vincristine; Mitoxantrone; Idarubicin; Bleomycin; Levoleucovorin; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I grade 3 follicular lymphoma; stage I adult diffuse small cleaved cell lymphoma; stage I adult diffuse mixed cell lymphoma; stage I adult diffuse large cell lymphoma; stage I adult immunoblastic large cell lymphoma; 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 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; 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; 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