BEAM vs. 90-Yttrium Ibritumomab Tiuxetan (Zevalin®)/BEAM With ASCT for Relapsed DLBCL
Condition: Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: 90-Yttrium Ibritumomab tiuxetan; Carmustine; Etoposide; Cytarabine; Melphalan; Autologous Hematopoietic Stem Cell Transplant; Rituximab
Intervention description: 0.4 mCi/kg given IV; Given IV; Given IV; Given IV; Given IV; Autologous Hematopoietic Stem Cell Transplantation (ASCT); Given IV
Intervention MeSH terms: Cytarabine; Rituximab; Etoposide; Melphalan; Carmustine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Non-Hodgkin's lymphoma; autologous stem cell transplantation; radioimmunotherapy; Zevalin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Immune System Diseases; Immunoproliferative Disorders; Lymphatic Diseases; Lymphoma, B-Cell; Lymphoproliferative Disorders; Neoplasms; Neoplasms by Histologic Type; Antibodies, Monoclonal; Immunologic Factors; Pharmacologic Actions; Physiological Effects of Drugs

Summary:

      This randomized phase III trial studies 90-yttrium ibritumomab tiuxetan and combination
      chemotherapy compared with combination chemotherapy alone before stem cell transplant in
      treating patients with diffuse large b-cell non-Hodgkin lymphoma that has returned after a
      period of improvement. Radioactive substances linked to monoclonal antibodies, such as
      90-yttrium ibritumomab tiuxetan, can bind to cancer cells and give off radiation which may
      help kill cancer cells. Drugs used in chemotherapy, such as carmustine, etoposide phosphate,
      cytarabine, and melphalan (BEAM), work in different ways to stop the growth of cancer cells,
      either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. It is not yet known whether 90-yttrium ibritumomab tiuxetan and BEAM before a stem
      cell transplant are more effective than BEAM alone in treating patients with diffuse large
      b-cell non-Hodgkin lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with CD20 positive diffuse large B-cell lymphoma as confirmed by a
             pathological biopsy report.

          2. Patients who are candidates for autologous stem-cell transplantation due to primary
             refractory or first relapse of disease.

          3. Patients must have chemo-sensitive disease achieving at least partial response (Cheson
             2007 criteria) to last chemotherapy.

          4. Patients with adequate autologous stem cell collection for transplantation (target >=
             2.5 x 10^6 CD34+ cells/kg).

          5. Patients must sign written informed consent.

          6. Adequate birth control in fertile patients.

          7. All prior chemotherapy completed at least three weeks before study treatment.

          8. Marrow involvement less than 25% at transplantation, no limitation on blood counts
             (low platelet count allowed).

          9. Negative HIV antibody.

        Exclusion Criteria:

          1. Chemo-refractory disease as determined by less than partial response (Cheson 2007
             Criteria) to last chemotherapy.

          2. Two or more relapses after initial response to induction chemotherapy.

          3. High-grade transformation from earlier diagnosis of low-grade lymphoma. Patients with
             "De Novo" Transformed DLBCL, defined as DLBCL only on lymph node biopsy and a
             discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are
             eligible if adherent to all other selection criteria.

          4. Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit.

          5. Creatinine > 2.0 mg/dl.

          6. KPS < 70.

          7. Uncontrolled infection.

          8. Pregnancy or lactation.

          9. Abnormal lung diffusion capacity (DLCO < 40% predicted).

         10. Severe cardiovascular disease; New York Heart Association (NYHA) Functional
             Classification ≥2.

         11. Active CNS disease involvement.

         12. Presence of any other malignancy or history of prior malignancy within 5 years of
             study entry. Within 5 years, patients treated for Stage I or II cancers are eligible
             provided they have a life expectancy > 5 years in relation to this prior malignance.
             The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ
             cervical cancer.

         13. Pleural effusion or ascites > 1 liter.

         14. Known hypersensitivity to rituximab.

         15. Psychiatric conditions/disease that impair the ability to give informed consent or to
             adequately co-operate.

         16. Prior radioimmunotherapy.

         17. Prior autologous or allogeneic HSCT.

         18. Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive.

         19. Patients who have had prior radiation to the lung will be excluded from the study,
             although mediastinal irradiation will be permitted if minimal lung is in the treatment
             volume.

         20. Patients who have received >500cGy radiation to the kidneys will be excluded from the
             study.