RATIONALE: Drugs used in chemotherapy, such as dexamethasone, cisplatin, gemcitabine, and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving rituximab as maintenance therapy after stem cell transplantation may kill any remaining cancer cells. It is not yet known which salvage chemotherapy regimen is more effective before autologous stem cell transplantation in treating relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying salvage chemotherapy using dexamethasone, cisplatin, and gemcitabine to see how well it works compared to dexamethasone, cisplatin, and cytarabine given before autologous stem cell transplantation in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. This trial also is studying giving rituximab as maintenance therapy to see how well it works compared to no further therapy after stem cell transplantation. Rituximab was added to both salvage treatment arms for CD20+ patients in a protocol amendment in 2005.

OBJECTIVES:

Salvage therapy

Primary

• Compare the response rate and transplantation rate in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma when treated with salvage chemotherapy comprising dexamethasone, cisplatin, and gemcitabine with or without rituximab vs a standard platinum-based regimen (dexamethasone, cisplatin, and high-dose cytarabine with or without rituximab).
• To compare the transplantation rates of the two protocol salvage regimens.

Secondary

• Compare the event-free and overall survival of patients treated with these regimens.
• Compare the success rate of these regimens, in terms of getting patients to autologous stem cell transplantation and successful mobilization after high-dose chemotherapy.
• Compare the quality of life of patients treated with these salvage regimens.
• Compare the toxic effects of these salvage regimens in these patients.
• Compare resource utilization for patients treated with these salvage regimens.
• Compare relative medical and societal costs of these salvage regimens with outcomes in these patients.

Maintenance therapy

Primary

• Compare the 2-year event-free survival of patients with CD20+ B-cell lymphoma treated with maintenance rituximab after these salvage regimens and autologous stem cell transplantation to those patients who received no further treatment.

Secondary

• Compare the 2-year survival of patients treated with or without maintenance rituximab.
• Compare the toxic effects of rituximab vs observation alone in these patients.

OUTLINE: This is a randomized, multicenter study. For salvage therapy, patients are stratified according to participating center, International Prognostic Index score at relapse/study entry (0 or 1 vs 2 vs ≥ 3), immunophenotype (B cell vs T cell), response to or response duration after initial chemotherapy (no response or progressive disease vs > 1 year vs ≤ 1 year), and prior rituximab (yes vs no). For maintenance therapy, patients are stratified according to participating center, salvage therapy treatment randomization (with or without rituximab, cisplatin, dexamethasone, and gemcitabine vs with or without rituximab, cisplatin, dexamethasone, and cytarabine), response to salvage therapy (complete response [CR] and CR unconfirmed [CRu] vs partial response [PR] vs stable disease [SD]), and prior rituximab (yes vs no).

• Salvage therapy: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.
  • Arm II: Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.

In both arms, treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are reassessed after 2 courses. Patients with progressive disease are removed from study. Patients with a CR, CRu, or PR proceed to autologous stem cell transplantation (ASCT). Patients with SD may proceed to ASCT or receive 1 additional course of salvage therapy at the discretion of the investigator. Patients receiving an additional course of salvage therapy are then reassessed after the completion of therapy. Patients with progressive disease are removed from study. Patients with a PR proceed to ASCT. Patients with SD may proceed to ASCT or be followed off study at the discretion of the investigator.

• ASCT: Responding patients (or those with stable disease, if that is the center's policy)undergo mobilization, stem cell harvest, and subsequent ASCT. Patients with CD20+ B-cell disease are randomized to maintenance therapy or observation.

• Maintenance therapy: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients undergo observation only. Quality of life is assessed at baseline, days 1 and 10 of course 2, day 1 of course 3 (if given), on the last day of salvage therapy (or the first day of mobilization, if given), and at 1 month posttransplantation.

Patients who undergo ASCT are followed at months 1, 3, 7, 13, 19, and 25 and then annually thereafter. Patients who complete salvage therapy, but do not undergo ASCT are followed at months 4, 8, 14, 20, and 26 and then annually thereafter. Patients who relapse or progress are followed every 6 months until 25 months from ASCT or 26 months from completion of salvage therapy and then annually thereafter.

PROJECTED ACCRUAL: A total of 637 patients will be accrued for this study within 3-4 years for the first randomization, and 240 transplanted CD20+ patients will be needed for the second randomization.

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes:

  • Diffuse large cell lymphoma (includes primary mediastinal B-cell lymphoma and T-cell-rich B-cell lymphoma)

  • Prior indolent lymphoma (e.g., follicular center cell lymphoma; marginal zone lymphoma, including extranodal mucosa-associated lymphoid tissue [MALT] lymphoma; and lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at relapse

    • Must be histologically confirmed
    • No transformed lymphoma at diagnosis with subsequent indolent histology without transformation at relapse

  • Peripheral T-cell lymphoma

  • Anaplastic large cell lymphoma

  • Small noncleaved Burkitt-like lymphoma

• T-cell or B-cell lineage confirmed by immunohistochemistry

• Clinically or radiologically documented disease meeting either of the following criteria:

  • Measurable disease, defined as at least 1 bidimensionally measurable site of disease using clinical exam, CT scan, or MRI

    • Lymph nodes must be > 1.5 cm by physical exam or CT scan
    • Other non-nodal lesions must be ≥ 1.0 cm by physical exam, CT scan, or MRI
    • Bone lesions are not considered measurable

  • Evaluable disease, defined as only nonmeasurable disease, including any of the following:

    • Marrow infiltration
    • Cytology-confirmed ascites or effusions
    • Bony involvement
    • Enlarged liver or spleen
    • Unidimensionally measurable intrathoracic or abdominal masses

• Previously treated with 1, and only 1, chemotherapy regimen including an anthracycline and excluding cisplatin, cytarabine, and gemcitabine

• No uncontrolled CNS involvement by lymphoma

  • No CNS disease at time of relapse
  • CNS disease diagnosed at initial presentation allowed provided a complete response for CNS disease was achieved and maintained

PATIENT CHARACTERISTICS:

Age

• 16 to 65

Performance status

• ECOG 0-3

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute granulocyte count ≥ 1,000/mm^3
• Platelet count ≥ 75,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 2.5 times ULN (5 times ULN if liver involvement with lymphoma)
• Hepatitis B status known (for patients with a history of hepatitis B or who are at high risk of hepatitis B infection)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No significant cardiac dysfunction or cardiovascular disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to complete quality of life questionnaires
• HIV negative
• No active, uncontrolled bacterial, fungal, or viral infection
• No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
• No other concurrent serious illness or medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Chemotherapy
• Prior rituximab allowed

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior IV chemotherapy
• No prior high-dose chemotherapy with stem cell transplantation

Endocrine therapy

• No concurrent corticosteroids except for physiologic replacement

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

  • Exceptions may be made for low-dose, non-myelosuppressive radiotherapy

• No prior radiotherapy to more than 25% of functioning bone marrow

• Involved-field radiotherapy may be given to areas of bulky disease at relapse (≥ 5 cm) after stem cell transplantation, according to the center's policy

Surgery

• At least 2 weeks since prior major surgery

Other

• No other concurrent anticancer therapy
• No other concurrent experimental agents