Yttrium-90 Ibritumomab Tiuxetan (Zevalin) With BEAM in Relapsed Low Grade B-Cell Lymphoma

The objective of this study is to evaluate the efficacy and the safety of Zevalin-BEAM preparative regimen before autologous stem cell transplantation (ASCT) as measured by the event free survival (EFS). The goal is to obtain a 15% increase of EFS at 2 years.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

Inclusion Criteria:

* Aged 18 to 65 years
* Patients with pathologically proven at relapse, low grade B-cell lymphoma CD20- positive (World Health Organization \[WHO\] classification):

  * Marginal zone;
  * Lymphocytic; or
  * Follicular.
* In relapse after complete remission (CR), less than partial remission (PR) or partial response (maximum of 3 lines of treatment)
* Previously treated with chemotherapy regimen with or without rituximab
* With a chemo-sensitive disease using salvage therapy
* Eligible for autologous stem cell transplantation
* ECOG performance status 0 to 2
* Minimum life expectancy of 3 months
* Negative HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies \< 4 weeks (except after vaccination)
* Signed informed consent form

Exclusion Criteria:

* Histological transformation in diffuse large cell from a low grade B-cell lymphoma
* Prior transplantation
* Contraindication to any drug contained in the chemotherapy regimens
* Large bone marrow irradiation \> 40%
* Bone marrow infiltration \> 25%
* Lack of sufficient autologous stem cells for transplantation
* Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study
* Any serious active disease or co-morbid medical condition (according to the investigator's decision and information provided in the Investigational Drug Brochure \[IDB\])
* Poor bone marrow reserve as defined by neutrophils \< 1.5 G/l or platelets \< 100 G/l, unless related to bone marrow infiltration
* Poor renal function (creatinine level \> 2.5 maximum normal level) unless abnormalities are related to the lymphoma
* Poor hepatic function (total bilirubin level \> 30 mmol/l, transaminases \> 2.5 maximum normal level) unless abnormalities are related to the lymphoma
* Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
* Presence of anti-murine antibody (HAMA) reactivity
* Known hypersensitivity to murine antibodies or proteins
* Pregnant women
* Adult patients unable to give informed consent because of intellectual impairment

• BACKGROUNDBrice P, Simon D, Bouabdallah R, Belanger C, Haioun C, Thieblemont C, Tilly H, Harousseau JL, Doyen C, Martin C, Brousse N, Solal-Celigny PH; Groupe d'Etude des Lymphomes de l'Adulte (GELA). High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol. Ann Oncol. 2000 Dec;11(12):1585-90. doi: 10.1023/a:1008399623564. PMID 11205467
• BACKGROUNDMills W, Chopra R, McMillan A, Pearce R, Linch DC, Goldstone AH. BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma. J Clin Oncol. 1995 Mar;13(3):588-95. doi: 10.1200/JCO.1995.13.3.588. PMID 7884420
• BACKGROUNDWitzig TE, White CA, Gordon LI, Wiseman GA, Emmanouilides C, Murray JL, Lister J, Multani PS. Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-hodgkin's lymphoma. J Clin Oncol. 2003 Apr 1;21(7):1263-70. doi: 10.1200/JCO.2003.08.043. PMID 12663713
• BACKGROUNDFung HC, Forman SJ, Nademanee A, Molina A, Yamauchi D, Speilberger R, Kogut N, Sahebi F, Parker P, Rodriguez R, Krishnan A, Popplewell L, Wong J, and Raubitschek A. A new preparative regimen for older patients with aggressive CD20-positive B-cell lymphoma utilizing standard-dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) radioimmunotherapy (RIT) combined with high-dose BEAM followed by autologous hematopoietic cell transplantation (AHCT) : targeted intensification without increased transplant-related toxicity. Blood 2003, forty-fifth annual meeting of the American Society of Hematology, abstract 870.
• BACKGROUNDNademanee A, Forman SJ, Molina A, Kogut N, Fung HC, Yamauchi D, Anderson A-L, Smith D, Liu AN, and Raubitschek A. High-dose radioimmunotherapy with yttrium 90 (90Y) ibritumomab tiuxetan with high-dose etoposide (VP-16) and cyclophosphamide (CY) followed by autologous hematopoietic cell transplantation (AHCT) for poor-risk or relapsed B-cell non-Hodgkin's lymphoma (NHL): update of a phase I/II trial. J Clin Oncol 2004, fortieth annual meeting of the American Society of Clinical Oncology, abstract 6504.