Rituxan/BEAM vs Bexxar/BEAM in Autologous Hematopoietic Stem Cell Transplant for Non-Hodgkin's Lymphoma (BMTCTN0401)
Condition: Lymphoma, B-Cell; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma
Intervention: Autologous transplantation using rituxan/BEAM; Autologous transplantation using Bexxar/BEAM
Intervention description: Rituxan 375 mg/m2 (Day -19 and Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation; Bexxar dosimetric dose 5 mCi (Day -19); Bexxar therapy dose 75 cGy TBD (Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation
Intervention MeSH terms: Rituximab; Tositumomab I-131
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 224.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Large B-Cell Lymphoma; Non-Hodgkin's Lymphoma

Summary:

      This study is designed as a Phase III, multicenter trial, comparing progression-free survival
      (PFS) after autologous hematopoietic stem cell transplantation using a standard Rituxan plus
      BEAM transplant regimen versus a regimen adding Bexxar to BEAM.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of persistent or recurrent REAL classification diffuse large B-cell
             lymphoma, composite lymphoma with more than 50% diffuse large B-cell lymphoma,
             mediastinal B-cell lymphoma

          -  Demonstration of CD20+ on at least one histologic specimen

          -  18-80 years old at time of first registration

          -  Three or fewer prior regimens of chemotherapy over the entire course of their disease
             treatment (including one induction chemotherapy and no more than 2 salvage
             chemotherapies); monoclonal antibody therapy and involved field radiation therapy will
             not be counted as prior therapies

          -  Disease status of primary induction failure, first relapse, or second complete
             remission; all patients must have chemosensitive disease as demonstrated by response
             to induction or salvage chemotherapy with at least a partial response (as defined in
             the protocol)

          -  No more than a 20% bone marrow involvement

          -  Patients with adequate organ function as measured by:

          -  Cardiac: American Heart Association Class I: Patients with cardiac disease but without
             resulting limitation of physical activity; ordinary physical activity does not cause
             undue fatigue, palpitation, dyspnea, or anginal pain; additionally, patients greater
             than 60 years of age must have a left ventricular ejection fraction at rest of at
             least 40% demonstrated by Multi-Gated Acquisition Scan (MUGA)

          -  Hepatic: Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia
             attributed to Gilbert syndrome) and alanine transaminase (ALT) and aspartate
             transaminase (AST) less than 3x the upper limit of normal

          -  Renal: Creatinine less than 2.0 mg/dL or creatinine clearance (calculated creatinine
             clearance is permitted) more than 40 mL/min; no hydronephrosis on CT scan prior to
             mobilization

          -  Pulmonary: Carbon Monoxide Diffusing Capacity (DLCO), Volume forcibly exhaled in one
             second (FEV1), forced vital capacity (FVC) at least 45% of predicted (corrected for
             hemoglobin)

          -  Autologous graft with a minimum of at least 1.5 X 10^6 CD34+ cells/kg (target greater
             than 2.0 X 10^6 CD34+ cells/kg. Peripheral blood stem cells (PBSC) are preferred;
             however, if PBSC mobilization fails, cells can be obtained by institutional practices
             (in cases where bone marrow will be used for transplantation, the required CD34+ dose
             does not apply and institutional practice for total nucleated cell dose should be
             used).

          -  Initiate conditioning therapy within 3 months of mobilization

          -  Signed informed consent

        Exclusion Criteria:

          -  Karnofsky performance score less than 70%

          -  Transformed follicular lymphoma

          -  Uncontrolled bacterial, viral, or fungal infection (currently taking medication and
             with progression or no clinical improvement)

          -  Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma
             in situ; cancer treated with curative intent less than 5 years previously will not be
             allowed unless approved by the Medical Monitor or Protocol Chair; cancer treated with
             curative intent less than 5 years previously will be allowed

          -  Pregnant (positive β-HCG) or breastfeeding; this patient population is excluded due to
             the lack of data on the use of Bexxar in patients who are pregnant or breastfeeding

          -  Seropositivity for HIV; this patient population is excluded due to the lack of data on
             the use of Bexxar in HIV positive patients and because the treatment regimens are too
             immunosuppressive for this patient population

          -  Fertile men or women unwilling to use contraceptive techniques from the time of
             initiation of mobilization until six-months post-transplant

          -  Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)

          -  Patients with evidence of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or
             abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow
             examination

          -  Patients with a prior severe reaction to Rituxan or Filgrastim (G-CSF). Patients with
             severe reactions to G-CSF that receive pre-medication for control of the reaction are
             not excluded from study.

          -  Patients who have received prior radioimmunotherapy

          -  Patients with known hypersensitivity to murine proteins