I am a physician-scientist committed to patient-oriented research involving radioimmunotherapy (RIT) for the treatment of non- Hodgkin's lymphoma (NHL). My immediate career development plans include specialized clinical research training in biostatistics, epidemiology, and clinical trial design at the School of Public Health at the University of Washington (UW), as well as didactic and mentored instruction in ethical aspects of clinical research, Quality of Life assessment, and research group involvement at the UW and Fred Hutchinson Cancer Research Center. The overall scientific objectives of this project are to expand and optimize RIT for the treatment of relapsed non-Hodgkin's lymphoma by (1) determining the toxicities and efficacy of myeloablative I-131- anti-CD20 antibody (Ab) combined with cyclophosphamide and etoposide and autologous stem cell transplantation (ASCT) in a Phase II trial for patients (pt) with relapsed NHL, (2) investigating the feasibility, tolerability, and potential efficacy of single agent myeloablative I-131-anti-CD20 Ab followed by ASCT in pt greater than or equal to 60 years old with relapsed NHL in a Phase I/II study, (3) assessing the quality of life (QOL) and neurocognitive function (NCF) of high dose RIT on pt treated in aims 1 and 2, and (4) performing pre-clinical and clinical studies of biological agents with minimal toxicity (cytokines and retinoids) to further augment the efficacy of anti-CD20 antibody therapy. We hypothesize that targeting radiation specifically to B cell lymphomas with I-131-anti-CD20 antibodies will augment the efficacy and decrease the toxicity of therapy compared with transplant regimens containing nonspecific external beam total body irradiation (TBI). We further postulate that I-131-anti-CD20 targeted RIT will improve the post- transplant QOL and NCF compared to those of pt transplanted with traditional conditioning regimens containing TBI (which deliver greater than or equal to 12 Gy to the brain). We anticipate that the tolerable toxicity of single agent I-131-anti-CD20 + ASCT (established in previous trials) will allow us to safely extend this potentially curative therapy to elderly pt who may not otherwise be eligible for stem cell transplantation. Finally, we hypothesize that augmenting CD20 antigen expression on malignant B cells with cytokines such as GM-CSF and enhancing anti-CD20 Ab mediated apoptosis with retinoic acid derivatives will amplify the cytotoxicity of both unmodified and radiolabeled anti-CD20 Ab.. We anticipate that these interventions will ultimately enhance the prognosis for patients with relapsed lymphoma by increasing the response and survival rates, while simultaneously minimizing toxicities.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Subcommittee G - Education (NCI)
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Gorelic, Lester S
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University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
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Hattori, Naoya; Gopal, Ajay K; Shields, Andrew T et al. (2012) 131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin's lymphoma: radiation dose to the testes. Nucl Med Commun 33:1225-31
Gopal, Ajay K; Press, Oliver W; Shustov, Andrei R et al. (2010) Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma 51:1523-9
Gopal, Ajay K; Pagel, John M; Fromm, Jonathan R et al. (2009) 131I anti-CD45 radioimmunotherapy effectively targets and treats T-cell non-Hodgkin lymphoma. Blood 113:5905-10
Till, Brian G; Gooley, Theodore A; Crawford, Nathan et al. (2008) Effect of remission status and induction chemotherapy regimen on outcome of autologous stem cell transplantation for mantle cell lymphoma. Leuk Lymphoma 49:1062-73
Gopal, Ajay K; Press, Oliver W; Wilbur, Shani M et al. (2008) Rituximab blocks binding of radiolabeled anti-CD20 antibodies (Ab) but not radiolabeled anti-CD45 Ab. Blood 112:830-5
Gopal, Ajay K; Metcalfe, Tracee L; Gooley, Ted A et al. (2008) High-dose therapy and autologous stem cell transplantation for chemoresistant Hodgkin lymphoma: the Seattle experience. Cancer 113:1344-50
Zhang, Michelle M; Gopal, Ajay K (2008) Radioimmunotherapy-based conditioning regimens for stem cell transplantation. Semin Hematol 45:118-25
Rajendran, Joseph G; Gopal, Ajay K; Fisher, Darrel R et al. (2008) Myeloablative 131I-tositumomab radioimmunotherapy in treating non-Hodgkin's lymphoma: comparison of dosimetry based on whole-body retention and dose to critical organ receiving the highest dose. J Nucl Med 49:837-44
Pham, R N; Gooley, T A; Keeney, G E et al. (2007) The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantation for follicular lymphoma. Bone Marrow Transplant 40:1039-44
Keeney, Grant E; Gooley, Ted A; Pham, Rosalyn N et al. (2007) The pretransplant Follicular Lymphoma International Prognostic Index is associated with survival of follicular lymphoma patients undergoing autologous hematopoietic stem cell transplantation. Leuk Lymphoma 48:1961-7

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