Despite dramatic advances in combination chemoimmunotherapy for newly diagnosed patients with non-Hodgkin's lymphomas (NHL), few patients with relapsed B cell NHL can be cured with conventional treatments. The primary objective of this project is to optimize the therapeutic utility of high dose radiolabeled monoclonal antibodies targeting the CD20 antigen in conjunction with autologous stem cell transplant (ASCT) for treating patients with relapsed or refractory B cell lymphomas. In this application, we propose four approaches to achieve this goal. First, we will conduct a disease-specific, phase II trial of (131)I-anti-CD20 antibody with etoposide (VP16), cyclophosphamide (CY) and ASCT to establish the efficacy of this regimen for treating three of the most common histologic subtypes of relapsed B NHL (Aim I). Second, we will explore the ability of a synergistic chemotherapeutic agent (fludarabine) to enhance the efficacy of (131)I-anti-CD20 antibody for older patients in the setting of ASCT (Aim II). Third, we will investigate the feasibility and safety of improving the specificity of radiation dose delivery to tumor sites using pre-targeting technology (Aim III). Finally, we will perform long-term follow-up of patients treated on prior Phase I & II trials with (131)I-anti-CD20 antibodies + ASCT to ascertain long term efficacy and delayed toxicities (Aim IV). This sequence of studies should enable us to achieve our long term objectives of further establishing and augmenting the role of high dose radioimmunotherapy and ASCT in the treatment of relapsed NHL.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA044991-18
Application #
6913345
Study Section
Subcommittee G - Education (NCI)
Project Start
2005-05-01
Project End
2010-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
18
Fiscal Year
2005
Total Cost
$184,655
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Budde, Lihua E; Wu, David; Martin, Daniel B et al. (2018) Bendamustine with rituximab, etoposide and carboplatin (T(R)EC) in relapsed or refractory aggressive lymphoma: a prospective multicentre phase 1/2 clinical trial. Br J Haematol 183:601-607
Greenbaum, Adam M; Green, Damian J; Holmberg, Leona A et al. (2018) Bendamustine, etoposide, and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in non-Hodgkin lymphoma. Blood Res 53:223-226
Green, Damian J; Press, Oliver W (2017) Whither Radioimmunotherapy: To Be or Not To Be? Cancer Res 77:2191-2196
O'Steen, Shyril; Green, Damian J; Gopal, Ajay K et al. (2017) Venetoclax Synergizes with Radiotherapy for Treatment of B-cell Lymphomas. Cancer Res 77:3885-3893
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Graf, Solomon A; Gopal, Ajay K (2016) Idelalisib for the treatment of non-Hodgkin lymphoma. Expert Opin Pharmacother 17:265-74
Chen, Robert; Gopal, Ajay K; Smith, Scott E et al. (2016) Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood 128:1562-6

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