Chemotherapy Before Autologous Stem Cell Transplantation +/- Rituximab in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: rituximab; cisplatin; cytarabine; dexamethasone; gemcitabine hydrochloride
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Cytarabine; Dexamethasone; Rituximab; Gemcitabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 849.0
Sex: All
Minimum age: 16 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: anaplastic large cell lymphoma; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; angioimmunoblastic T-cell lymphoma

Summary:

      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.
    

Eligibility criteria:

        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