S1106 Rituximab With Combination Chemotherapy or Bendamustine Hydrochloride Followed by Consolidation Chemotherapy and Stem Cell Transplantation in Older Patients With Previously Untreated Mantle Cell Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: rituximab; bendamustine hydrochloride; cyclophosphamide; cytarabine; dexamethasone; doxorubicin hydrochloride; leucovorin calcium; methotrexate; vincristine sulfate
Intervention description: Given IV; Given IV; Given IV; Given IV; Given PO or IV; Given IV; Given PO or IV; Given IV; Given IV
Intervention MeSH terms: Leucovorin; Cytarabine; Dexamethasone; Cyclophosphamide; Bendamustine Hydrochloride; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma

Summary:

      RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different
      ways. Some find cancer cells and help kill them or carry cancer-killing substances to them.
      Others interfere with the ability of cancer cells to grow and spread. Drugs used in
      chemotherapy also work in different ways to kill more cancer cells or stop them from growing.
      It is not yet known whether rituximab is more effective with combination chemotherapy or
      bendamustine hydrochloride in treating patients with mantle cell lymphoma undergoing
      peripheral blood stem cell transplantation.

      PURPOSE: This randomized phase II trial studies how well giving rituximab together with
      combination chemotherapy or bendamustine hydrochloride followed by consolidation chemotherapy
      and peripheral blood stem cell transplantation works in treating older patients with
      previously untreated mantle cell lymphoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  All patients must have previously untreated stage III, IV, or bulky stage II mantle
             cell lymphoma (MCL)

               -  A diagnosis of MCL must be confirmed by histopathological diagnosis including
                  immunohistochemistry and flow cytometry documenting both of the following
                  phenotypes:

                    -  CD19+ or CD20+

                    -  Cyclin D1+ or evidence of the t(11;14) translocation by cytogenetics or FISH

          -  Adequate sections from the original diagnostic specimen must be available for
             submission for central review

               -  An adequate biopsy requires sufficient tissue to establish the architecture and a
                  WHO histologic subtype with certainty

                    -  Core biopsies, especially multiple core biopsies, MAY be adequate, but
                       needle aspirations or cytologies are not adequate

               -  Bone marrow core biopsy or clot sections (not aspirates) may be used as
                  diagnostic material if it is significantly involved and are the only diagnostic
                  material available

          -  All patients must have bidimensional measurable disease documented on the Lymphoma
             Baseline Tumor Assessment Form (Form #48031)

               -  Patients who also have non-measurable disease in addition to measurable disease
                  must have all nonmeasurable disease assessed within 28 days prior to registration

          -  Patients must not have clinical evidence of central nervous system (CNS) involvement
             by lymphoma

               -  Any laboratory or radiographic tests performed prior to registration to assess
                  CNS involvement must be negative

          -  Patients must have a unilateral/bilateral bone marrow aspirate and biopsy for staging
             performed within 42 days prior to registration

               -  If the biopsy cannot be performed but the aspirate is unequivocally consistent
                  with mantle cell lymphoma, this will be considered adequate for staging purposes

          -  Patients must be eligible for stem cell transplantation by institutional guidelines
             with the plan that transplant will be conducted at a cooperative group-approved
             transplant center

               -  Patients must be planning to undergo stem cell transplantation within 84 days
                  after day 1 of the last induction course

               -  Patients must have had at least 1.5 X 10^6 CD34^+ cells/kg collected and stored
                  prior to second registration for stem cell transplantation

        PATIENT CHARACTERISTICS:

          -  Zubrod performance status of 0-2

          -  Bilirubin ≤ 3 times upper limit of normal (ULN)

          -  Serum creatinine ≤ 2.0 times ULN

          -  Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 times ULN

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  Platelet count ≥ 100,000/mcL, unless due to bone marrow infiltration by lymphoma

          -  All patients ≥ 45 years of age must have an echocardiogram (ECHO) or Multi Gated
             Acquisition Scan (MUGA )scan within 42 days prior to registration (whichever method is
             used at baseline must be used at restaging)

               -  Patients < 45 years of age should have ECHO/MUGA only if clinically indicated

               -  Patients with an ejection fraction < institutional lower limit of normal (ILLN)
                  are not eligible

          -  Serum Lactate dehydrogenase (LDH) and a Complete Blood Count (CBC with differential
             must be measured within 28 days prior to registration

          -  Patients known to be HIV positive, or who have a history of solid organ
             transplantation, are ineligible

          -  No active hepatitis

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated
             Stage I or II cancer from which the patient is currently in complete remission; or any
             other cancer from which the patient has been disease-free for 5 years

          -  Pregnant or nursing women may not participate

          -  Women or men of reproductive potential may not participate unless they have agreed to
             use an effective contraceptive method

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics